[Music] hello everyone a very good evening to all of you I hope I'm clearly visible audible so I welcome you all for today's session I am Dr Priyanka sdv here and today we all gathered here to study leukemias right so let me see if everything is good to go everything is visible audible just a second let me see okay I guess it's clearly visible okay hello so today we are going to discuss the leukemias do you find leukemias difficult yes or no do you find it difficult let me ask the same question after 2 hours so in the two hours I'm going to make leukemia a cakewalk for you or fun for you let me ask the same question do you find leukemia difficult at the end of the session after two hours okay so today in this session we are going to compare the four leukemias that is CML AML Al and cl in the most simplified possible manner in this world so uh you will find this session very interesting very useful whatever exam you are targeting for if you are a second Prof student and you are targeting for your uh University exam in pathology or you are in a final year and you are targeting your medicine exam so in the hematology section the leukemias will be useful for you and if you are an intern or post intern and you are targeting for any of the competitive exam like NE PG fmg in C usml plab the session is going to be ultra useful for you so whatever section you take the leukemia is is a very important topic and students find it difficult so without wasting any further time I guess I must start so let's start with lemas so let me start let me share my screen with you give me a minute to share my screen with you I guess you can see my screen so let's start the topic that is l leukemia okay so leukemia is basically everyone knows it's a blood cancer so it is a disorder of blood it's a disorder of blood in the blood basically it's the disorder of WBC so if you want to understand every depth in leukemia you must understand wbc's first if you don't understand how does the WBC formed in the bone marrow what are the precursors of WBC you can't understand leukemia so let me start from the basic I'm assuming that you don't know you know nothing about the leukemias I'm starting from the scratch and I will take you to the super epic of the leukemias let's start from the scratch okay so let's start it okay yes so let's start so as I told you leukemia is a disorder of WBC so let's first in the five minutes let's see how does the wbcs are formed okay what are wbcs white blood cells they are they are they are the lucos sides how many type of WBS are present in human there are five type of wbcs there are five type basically there are of two type the granulocytes and a granulocytes granulocytes are the WBC they have granules present in their cytoplasm that's why they are known as granulites and a granulites are the WBC they don't have any granules in the cytoplasm that's why they are known as a a means absent absent the granules are absent so three of them are granulocytes what are the three type of granulites neutrophil eosinophil basophil neutrophil have pink or purple granules in the cytoplasm I appreciate it eosinophils have brick red color in the cytoplasm granules in the cytoplasm brick red color appreciated and basophils have dark blue or black color granules in the cytoplasm but the common thing is that they all have granules in the cytoplasm got it these are the granulites coming on a granulocytes they don't have granules in the cytoplasm obviously that's why they are known as a granulocytes so these are of two type lymphocytes we can see the nucleus and hardly any cytoplasm you can see scanty cytoplasm and the second is monoy you can see the nucleus is Horseshoe shape it is horseshoe shaped nucleus sometime kidney shaped nucleus is there and this is monoy but you appreciate in the cytoplasm there are no granules these two are adrenal sites okay we got it so total five type of wbcs are there we got it granulocytes these are of three type and a granulocytes these are of two type so it is neutrophil eosinophil basophil V seen and agyes may we have lymphocytes and monocytes so total WBS are there now the next question where does they formed where does they form tell me the organ of course they all are formed in the bone marrow let me show you how does they form so you see this is the bone marrow in the bone marrow all the blood cells are formed rbcs wbcs as well as plates all the blood cells are formed in the bone marrow so in the bone marrow the first cell which give rise to all the blood cells is known as hematopics stem cell I call it the Father the ancestor of all cell the hematopoetic stem cell is the father or the ancestor of all the blood cells so let me tell you this is the hematopoetic stem cell present in the bone marrow now from this hematop stem cell you can see the two arrows are coming so two cells are formed one is myoid stem cell or myoid progator or one is lymphoid stem cell or lymphoid progator so you can see myoid progator and lymphoid progator progator is the stem cell so it give rise to two stem cells two lineage two stem cells one is myoid stem cell one is lymphoid myoid progenitor lymphoid progator now how many type of blood cells are there say ma'am there are three types of blood cells we have rbcs known as erthrocytes we have platelets okay which are known as Mega caroy and we have WBC that is Lucy so we have arthrite mega caroy and Lucy the three type of blood blood cells and the wbcs are of five types we have already seen so total 5 + 1 plus 1 so total seven type of blood cells are present we have to form all the seven that is five WBC one RBC one PL from these stem cils so how does they formed how does they formed please understand first if you have any query please write down in the chat box I'm having an eye on the chat box also but if I'm in the middle of something I'm explaining you I will not interrupt that let me finish that portion and I will come on your queries so don't worry if you have any query just text it here and as soon as I finish that something I'm explaining you after that I will come on your queries also okay okay listen now so as I told you there are two type of progenitor myoid progator and lymphoid progator so myoid progator give rise to rbcs all rbcs it give rise to all platelets also all platelets and there are five type of WBC out of the five type of WBC you know there is a cell which is formed Here is known as myoblast this myoblast give rise to four type of WBC which four neutrophil eosinophil basophil and monoy but not lymy so all the rbcs are formed from myoid all the platelets are also formed form from myoid series out of the five WBC four of them are formed from the myoid now the one is spending only one that is lymo side that will be formed from lymphoid the lymphoid progenitor so same thing is written in front of you please understand please understand if you don't understand things you will not be able to understand the different type of leukemias please understand from the basic so you can see it here there is myoid progator which give rise to all RBC because it will give rise to erythroid precursor it will give rise to RVC the platelets are also formed from the myoid precursor only myoid progenitor and here is a cell formed which is known as myoblast what's the name of the cell myoblast myoblast give rise to four WBC out of the five WBC four are formed here neutr eosinophil basophil and monoy but not the lymphocyte so only one cell so out of the seven cells six are formed here only the last one the the seventh one it will be formed from the lymphoid progator lymphoid stem cell it give rise to lympho blast and it give rise to lymphocytes and maximum WBC I will use the word maximum that is four out of five so four out of five that is maximum WBC are formed from the myoid progenitor so can I call the myoid progenitor as trilineage can I call say yes or say no yes it is a trilineage trilineage means it is giving rise it is giving rise to three type of cells it is giving rise to rbcs also it is giving rise to platelet also and it is giving rise to maximum WBC also this one is not Trine age and here I guess you all can appreciate two type of blast are formed you have to understand the meaning of the blast Milo blast and lympo blast Milo blast is from myoid progenitor lymphoblast is from lymphoid progenitor myoblast give rise to these WBC and lymphoblast give rise to lympo lymphocyte only currently I'm not interested in RBC I'm not interested in plat late to whom I'm interested I'm teaching you leukemia so I'm interested in wbcs only so wbcs all five wbcs are formed from blast so you can see this is the thing I taught you till now you can see this is the hematopics cell it give rise to two stem cells myoid stem cell and lymphoid the myoid is giving rise to rbcs it is giving rise to platelet and it is giving rise to four WBC out of five and the lymphocytes are arising from the lymphoid stem cell the same is shown to you in this figure also okay now the point is that they are not formed directly listen listen listen I am interested in WBC as I told you so I want to teach you how does the lymphocytes are formed it is not directly that lymphoblast give rise to lympo lymphoid there are certain precursors in between you have to write down you have to learn the intermediates the same here also I will I will not teach you all four I will take the Prototype as neutrophil so I want to tell you how does neutrophil is formed from The myoblast Tell me the intermediates here so in the same way eosinophil BAS and monocytes are also formed but we will not see all so I want to teach you two cells in detail the neutrophil how does they form from the this myoblast and the lymphocytes how does they form from the lymphoblast you have to understand the intermediates in between which are known as precursors if you have understood this believe me leukemia will become a cakewalk for you believe me got my point so you can see this is a precursors in between it looks complicated don't worry let me simplify it let me simplify it so I will simplify it so let's take neutrophil from here I will tell you the precursors and let's take the lymphocyst of these three they are likewise the same as that of neutrophil only so we will take a prototype from here that is neutrophil the point is that the neutrophil is formed from the myoblast and there are many intermediates in between and the lympho is formed from the lymphoblast and there are certain intermediates in between we have to see that intermediates which are known as precursors got it now see let's start from the beginning so again you can see this is hematopoetic stem cell so two blast are there Milo blast lymphoblast okay let's take myoblast first okay I want to tell you from the myoblast how does neutrophil formed tell me the intermediates there are five intermediates in between you have to learn the name of the connecting intermediates from the myoblast to neutrophil learn it so from the Milo blast the first cell which is formed is prosite then it is myosite then it is metam miloy then it is band form and finally neutrophil so please learn the precursors so what are the precursors first is myoblast then prosite myosite metam miloy you can say it together prosite myosite metam myoy then band form and finally neutrophil in the same way eosinophil basophil and monocytes are also formed we will not see their precursors coming on the other side you can see we have a lymphoblast here lymphoblast give rise to lympo side but only one intermediate is there there are not five intermediates only one prolymphocytic stem cell it gives rise to two blast you have to understand blast what is blast we have two blast Milo blast lymol blast okay myoblast give rise to neutrophil okay I know it's also eosinophil basophil and monoy but I'm interested in neutrophil right now and lymol blast give rise to lymy tell me the intermediates who will tell me the intermediates myoblast prosite miloy metam myoy band form and finally neutr okay here lymphoblast only one prosite and finally lymy that's it if you have understood this if you have learned this let's move ahead now you are ready to start with the leukemia if you have understood the basics the same thing is written in front of you you can see you can see myoblast it give rise to prosite Milo blast it give rise to prosite then myosite then metam myosite then band form then finally neutrophil and you can see the lymphoblast this one is lymphoblast lymphoblast this is prosite and this is mature lymphocytes the B lymy and T lymy these are the two types everyone give me a thumbs up in the chat box if you got the basics if you got the basics everyone give me a thumbs up in the chat box please I request so if you got this we will start leukemias right now that was the overview now you can understand what is leukemia what is blood cancer how many of you got it give me a thumbs up come on if you have any doubt please you are open to ask don't hesitate if you have any doubt till now please ask it because if you don't understand this now there is no use of the next ahead to hour sitting here and watching it or listening it because the complete leukemia is based on this only everyone got it so kindly give a guesture that you got it come on can we go ahead okay so let's start it so I told you this is the precursor now this is our Master diagram in this diagram only I will teach you the four type of leukemias now listen I told you this is happening in the bone marrow this is bone marrow and this is blood this is blood vessel so in my bone marrow all these cells are present these all are present these all are present in my bone marrow hoptic stem cell is present which is giving rise so all the precursors are present in my bone marrow but in my blood who is coming only the mature versions The immature versions do not come in the blood only the mature forms so from here neutrophils are coming along with neutrophils I know neutrophil eosinophil basophil monoy I will consider all they all are coming okay but the mature forms and from here lymphocytes are coming my point is that these are the mature sells I mean to say please understand immature forms do not present in blood but they are present in bone marrow they are not present in blood but they're present in so if you check my bone marrow or any healthy human bone marrow you will find all these but if you check my blood or any healthy human being blood who don't have any blood disorders any WBC disorders you will find the mature uh wbes in their blood but not the immature one okay so this is the basic now what is leukemia this is leukemia leukemia is arrival of immature form especially the blast in the blood so once the blasts are coming in the blood oh my God blast which blast myoblast and lympo blast if they are coming in the blood it's leukemia the immature blast are coming in the blood in acute Le there are two type of leukemia acute and chronic in acute leukemia the blast the blast is the first cell the first cell is the blast myoblast and lymphoblast they are coming in the blood in acute leukemias in chronic leukemias the late later precursors can also come in the blood but it is the precursors which are coming in the blood so whatever is the leukemia it is the precursors which are coming in the blood except clll in CL blasts do not come in CL matal lymphocytes are there which become abnormal because of the mutation but in most of the leukemia the blasts are coming in the blood so immature forms are coming in the blood now you may be thinking Ma'am why why they are coming in the blood usually they don't come in the blood usually the mature forms are coming in the blood now you told us in a healthy human being the mature forms are coming in the blood what why these blast are coming in the blood we understood that once the blast are coming in the blood it's leukemia we understood that but the question arises in your mind is why you should ask this question why they are coming so the answer is mutation so in myoblast or in lymphoblast or in the other precursor cells there are certain mutations which are taking place mutation I will tell you the exact mutation also certain translocation certain deletion certain mutation in various leukemia the mutations are different now because of them they become cancerous cell and they start doing uncontrolled mitosis you know uncontrolled mitosis is the Hallmark of cancer once the cell have the mutation and because of that mutation if the particular cell get converted into a cancer cell that cell will do uncontrolled mitosis and replace all other cell example if this myoblast imagine this myoblast it is having certain mutation because of physical chemical or biological carcinogen this myoblast have certain mutation okay not other any other cell only this myoblast has certain mutation so this myoblast will do uncontrolled mitosis and it will replace all other cell and it will be spilled over in the blood I I'm using the word spilled over it will be spilled over in the blood because it is too high normally don't come in the blood but sometime if it is it is too high it is doing uncontrol mates it will be spilled so this cancer is known as AML sometime lymphoblast do so there is mutation in the lymphoblast so lymphoblast will do the uncontrolled mitosis and it is spilled over in the blood that is Al sometime all these cells will do uncontrolled mitosis they all are spilled in the blood myoid myoid precursors it is known as CML so different cancers have different type of mutation ultimately they convert into cancer cell and because they convert into the cancer cell they do uncontrolled mitosis and because of the uncontrolled mitosis they are spilled in the blood and once they are spilled in the blood it is known as leukemia the blood cancer the blood cancer actually the disorder is not in the blood it's a misnomer you can say the disorder is in the bone marrow so leukemias are the disorders of the bone marrow there's a disorder in the bone marrow in the bone marrow certain mutations are taking place because of which the blast or the precursors are spilled in the blood how many of you got it that is the basic that is the basic okay now listen listen one step further what ahead these blast are coming in the blood sometime they remain only in the blood okay like The Chronic leukemias they remain only in blood chronic myoid leukemia as well as chronic lymphoid CML as as well as CL they remain in the blood okay but sometime in certain leukemias after coming in the blood they enter into the solid organ and form the discrete masses in many solid organs like lever like spleen like lymph nodes producing producing various discrete masses so leukemias can give rise to lymphomas not always not always sometimes it is not necessary that all Leukemia convert into lymphoma not no sometime they do so and not all Leukemia it happens in AML it happens in Al like more frequently but not in others CML May don't happens how many of you got it how many of you got it so sometimes leukemias can give right lymphomas not always mind my words so this is the basics if you got so this is known as organ infiltration organ infiltration so normally the summary is that the normally the blasts are present in the bone marrow I'm I'm a healthy human being I don't have any WBC Disorder so in my bone marrow the blasts are there Milo blast is also there lympo blast is also there but they are present in my marrow they are not present in my blood they are not present in my organs if the blast if the myoblast or lymphoblast they because of the mutation they become cancer cell and they do uncontrolled mitosis because of the uncontrolled mitosis they become too high in number they replace all other cells and they are spilled in the blood once the blast come in the blood it is known as leukemia in the acute leukemia sometimes in chronic leukemia along with the blast the the immature versions also come okay the later precursors also come this is the early precursors in the series the earliest precursor in the series is blast got my point and after coming in the blood but not always sometimes they infiltrate in various organs and Leukemia can convert into lymphoma sometime not always mind my words I hope you all got it I hope you all got it say yes if you got it so let's classify leukemia let's classify leukemia it's very easy listen listen now the complete thing is depending which blast is coming which blast is coming this is a simplified version of leukemia I'm telling you the classification which blast is coming is it lympo blast or is it Milo blast which blast is coming if lympho blast is coming in the blood it's known as lymphoid leukemia the leukemia is lymphoid if Milo blast is coming it's myoid it's myoid lukemia okay one of the blast is coming in the blood lymphoid lymphoid blast is coming lymphoid leukemia myoid Blaster is coming myoid leukemia each of them can be acute can be chronic can be acute can be chronic so basically we have four types four types of leukemia what are the four types of leukemia can you say can you see the names say acute lymphoblastic leukemia Al chronic lymphocytic leukemia CL okay acute myoid leukemia and chronic Milo myoid leukemia so you can see Al CL AML and CML how many of you got it these two are myoid in origin and these two are lymphoid in origin so total four leukemias are there in our syllabus we will compare them one by one no it is not always I'm seeing that s bisma s is saying that lymphoma is always after leukemia no it's not necessary sometime the blast originate in the solid organs so lymphoma is the first thing happening and it will spilled over in the blood leading to the leukemia it is not necessary that leukemia give rise to Le lymphoma sometime lymphoma can also give rise to leukemia and sometime they are Deno only leukemia is there or only lymphoma is there it is not necessary that they are occurring together my point is that in leukemia it's a blood cancer you will not find any discrete mass in any organ but in lymphomas you will find the discrete masses in various solid organs so lymphoma is a tumor of solid organ but leukemia is a cancer of the blood how many of you got it you got it BMA you got it okay there can be other reasons also for the lymphoma so I will take one session on the complete lymphomas so I will schedule all lymphomas in one uh shot because many students after this session have demanded that ma'am after leukemias we want one session on lymphomas also Hotchkins Lymphoma as well as non- hotchkin lymphoma all lymphoma in one shot I'm going to schedule it do you want it if you want it we will schedule it soon okay very soon we will schedule it so let's continue with the leukemias right now okay so this is the classification of the leukemias you can see leukemias is of two type lymphoid and myoid here lymphoblast is coming and here Milo blast is coming in the blood each of them can be of two two type acute chronic acute chronic so finally we are having four types Al CLL AML and CML these two are myoid you can see myoid and these two are lymphoid so these are the four types what are acute and chronic in acute in acute glucemia whether it is myoid or whether it is lymphoid the blast are coming either Milo blast is coming or lymol blast is coming how much blast is coming so I told you now this is the Milo blast normally in the bone marrow in the bone marrow this is a myoblast this is a lymphoblast the blast are less than 5% normally in a healthy adult human being the blast are less than 5% now due to mutation either myoblast is doing uncontrolled mitosis or due to mutation lymphoblast is doing uncontrolled mitosis so if their percentage become more than 20% of all the cells more than 20% if each of them can be more than of 20% it is known as acute leukemia so the definition the wh criteria for leukemia is blast more than 20% you may be asking ma'am which blast it can be Milo blast it can be lymol blast each any of them so if myoblast is more than 20% I will call it AML acute myoid leukemia if lymphoblast is more than 20% I will call it Al so this is the definition of the acute leukemias please learn it by heart how many of you got it so this is the wh criteria wh criteria is more than 20% and Fab criteria you know there are two different organization wh and French American British so both of them now some some people follow this classification some follow so wh has given a cut off of 20% if the blast in the marrow is more than 20% it is known as acute leukemia if the blast is more than 30% it is known as acute leukemia this is according to Fab so according to wh the cut off is 20% and according to Fab French American British it is 30% so anyone can be asked in your exam so two different bodies have given two different cut off okay so usually we we consider the wh so please according to wh the criteria for the acute lemia is 20% blast minimum 20% more than 20% okay normally it is less than 5% how many of you got it got it so this is the definition of acute leukemia I taught you two definition acute myoid leukemia that is myoblast are more than 20% and acute lymphoid leukemia that is lymphoblast are more than 20% got it so that is the thing chronic lukemia May in chronic leucemia blast may come but basically the later precursors come in the blood so there is no cut off in The Chronic glucemia and each of them can be myoid lymphoid myoid lymphoid so AML is acute myoblastic glucemia Al is acute lymphoblastic leukemia CML is chronic myoid leukemia and cl is chronic lymphocytic leukemia so that is the thing we got it so ultimately the thing is which blast is coming in the blood so you should be to differentiate what is coming in the blood is it myoblast or lymphoblast both of them look differently so you should be aware of the morphology how does myoblast look and how does the lymphoblast look you must be aware of that how does myoblast look and how does lymphoblast look you should be aware of that got it so you should be aware of the morphology of both of them got it myoblast is little bit larger and lymol blast is little bit smaller you can see in the diagram itself don't learn see in the diagram here the cytoplasm is moderate you can see moderate amount of cytoplasm you can appreciate but hardly any cytoplasm you can see a peripheral Rim small rim of cytoplasm it's smaller with no cytoplasm or scany cytoplasm the most important difference here is the IOD here iur rods are may be present not always but you can find the I rods here I rods are always absent iur Rod is a red color Rod like thing which is a concentrate of the granules the granules are aggregating and forming a rod like material which is known as iur Rod so iur Rod is present in myoblast they are not present in lymphoblast please learn I Rod is the biggest difference you can see okay got my point got my point so that is the thing you can see here so that is the classification now we have four type of leukemia to be covered now so I request all my dear student to take out your notebooks to take out your pen and make this comparative table with me I will teach you four leukemias one by one in a fixed set of headings I will start with CML okay then I will teach you AML so myoid will be done first we will deal with the myoid these two are myoid leukemias then we will come on the lymphoid ones in the lymphoid one first I will teach you acute and then chronic so sequence is this because I want to compare these two the acute versions of the two together that's why first I'm telling you the myoid one first chronic then acute and then the lymphoid one first acute then chronic so this will be my sequence because I want to compare these two back to back that's why I'm telling you this sequence now in each of them first I will let you know the definition of each of them you should understand age group is very different so you know you get mcqs and you get a age So reading the age only in your question will give you you know a differential diagnosis they are talking about which type of leukemia so you have to concentrate on the age age is always important the most important is the mutation which exact mutation is there in each of them you have to learn the mutations then classification if applicable so I will tell you the fap classification here and here AML and the fap classification you have to learn French American British classification clinical features you have to understand lab diagnosis you get many questions on that treatment part I will deal here only the medicine part also and the prognostic factors you get many mcqs on prognosis believe me and not only this in the end we are going to compare all okay got my point we are going to compare all food together at one place in one shot so that the thing will be oversimplified so if you make this table with me it will be useful for you that after the session you can revise all the leukemias in just five minutes by looking at this table I can guarantee you all your mcqs can be cracked from this table take my challenge okay so let me summarize it and it will be given in the notes also after the session I'm going to provide you the PDF if you don't want to make this table it's okay it will be provided in the PDF so it's your choice so can we go ahead can we start so let's start with the first one let's start with the first one CML let's start with CML can I start so let's start with CML the first one so what's the definition of CML let's start with the introduction the definition of the CML what is CML there are four criterias if any human being any adult person a what is the normal WBC count in our blood we have RBC we have platelet and we have WBC this is the normal three cells present in the blood tell me the normal count of all three normal adult human being normal so rbcs are 4.5 to 5.5 million per microl or per deciliter okay platelet is 4 to 5 4 to 5 lakh not Mill ion lakh per deciliter wbcs are 4,000 to 11,000 per decil now see see the normal range the wbcs are in, 4 to11 the platelets are in lak okay 4 to 5 lakh and I'm sorry not 4 to 5 you can say 1.5 to uh 4 lakh 1.5 to four lakh I'm sorry and here the rbcs are 4.5 to 5.5 million per deciliter so that is per deciliter you can see now I'm concerned with WBC right now okay in all the leukemias and most of the leukemias the WBC count will be high that is known as three lakh like that so it is high it is high but these are not mature these are the immature one not the mature mature neutrophil eosinophil basophil monoy they're very Less in number very less but their precursors are more okay so that is the first criteria that is the first criteria so in total count total lucite count TLC the count is high and in DLC you will find these are immaturities these are not the mature one the first criteria Bops are too high the spomal is there the patient spleen is enlarged and Philadelphia chromosome is positive in 95% of the patient Philadelphia positive what ises Philadelphia I will tell you so learn the fourth criteria of CML so introduction May I'm sorry introduction May write down the four criteria the four criteria of CML you should know the four criteria you get a c on the criteria also so there are four criteria what are the four criteria number one WBC count is high lucco yosis with immaturities with immaturity the first foremost most important criteria out of which Bops are there Basils are really high number three spleen is enlarged spleen is there number three and number four Philadelphia chromosome is positive I will tell you what is it wait a while okay that is the four criteria what about the age it occurs in middle age or old age after 50 years usually after 50 years usually so you will get a question there is a 50 year 55 year 60 year male female whatever like that so middle to old age so it is after 50 years now coming on the pathogenes look at here everyone here on the screen I am teaching you CML I'm teaching you the path penesis of CML so it is a leukemia arising from the myoid origin so here the problem here in this precursors will be there the problem is not there in the lymphoid precursor the problem will be in the myoid precursor that we got it okay we got that now what are the myoid precursor we have five precursors we have myoblast prosite myosite metam myoy band form and neutrophil these are the cells you can see these are the cells these all cells have the nucleus and inside the nucleus they have the DNA now because of physical chemical or biological agents they got mutated they all got mutated they all got mutated not tell me this is a human cell any human cell this can be any human cell okay this is the nucleus of the human cell how many chromosomes we have we all know that we all have deployed cells that is 46 chromosome say yes or no instead of saying 46 chromosome why don't you say 23 pairs 23 pair is a better thing to say so this is pair number one pair number two pair number three pair number four five likewise 23 pairs are there I'm not interested in all pairs I'm interested in two pairs pair number 9 and 22 so on the next page I'm drawing two pairs okay so let's draw a cell okay let's draw the nucleus of the cell inside the nucleus I'm drawing only two pairs this is pair number nine and this is pair number 22 I'm interested in two which two this is nine this is 22 okay you will say m'am which cell is it which cell it can be one of the five cell I don't know it can be Milo blast it can be prosite it can be myosite it can be metam myosite it can be band form the mutation is occurring in all five in all five the five precursors of the myoid series okay so listen what is happening normally in me in you in all the adult human beings healthy human beings on chromosome number nine there is a gene the name of that Gene is albl that is a gene that is normal it is present in me you everyone the name of that Gene is Al Gene we all have that it's normal so it is doing its normal function the the normal function is mitosis but under control so whenever the growth factor is coming then only the cell is dividing otherwise cell is not dividing because of Al on 22 we have another Gene the name of that Gene is BCR we also have it have it I have you have we all have it it is also a normal Gene so again here it also helps in mitosis this also helps in mitosis this also helps in mitosis but mitosis under control so whenever the growth factor will come then only they will do the mitosis otherwise they will not do the mitosis now due to physical chemical or biological agents there is translocation what is translocation a portion of the two chromosome they will exchange with each other so here nine will give this portion to 22 which contain the albl so Al which is normally present in nine it is going to 22 it is going to 22 so Al will reach here abl will reach here and it will fuse with BCR BCR is already present on 22 so a will fuse with BCR say yes albl will be fusing with BCR so a new Gene is formed the fusion Gene it is known as as Fusion Gene albl BCR Fusion gene or albl BCR hybrid Gene Fusion or hybrid Gene that will lead to uncontrolled mitosis not this cell is cancer cell because of this deadly Gene this deadly Gene the fusion gene or hybrid Gene it will form an abnormal enzyme the name of that enzyme is tyrosin kyes tyrosin Kines abnormal tyrosin Kines that will do the uncontrolled mitosis this will go on dividing go on dividing from 1 to 2 2 to 4 4 to 8 8 to 16 16 to 32 32 to 64 so on on and they will be spilled in the blood so all these cells will be spilled in the blood got my point normally they are not present in blood they're present in Marrow but they will replicate replicate they will do the mitosis they will F the marrow they will replace all other cells in the marrow and after filling the marrow completely they will be spilled in the blood got my point this is CML you will you should be thinking ma'am that you said that it's translocation translocation is balanced here so here 9 is giving Al to 22 what 22 is giving to 9 22 is giving to nine a portion of chromosome which don't contain any important Gene which don't contain any important Gene so that portion is given to nine so basically the fusion is formed on 22 the fusion Gene that's why chromosome number 22 is known as Philadelphia chromosome Philadelphia chromosome this chromosome is known as Philadelphia chromosome because the fusion Gene is formed here got my point how many of you got it so this is the fusion Gene which is formed on 22 so on chromosome number 22 in a patient with CML we get a gene that is a hybrid Gene of fusion Gene where the two genes are fusing with each other Al and BCR normal adds don't have this Fusion Gene I'm having Al but my Al is on nine I'm having 20 um BCR but it's on my 22 I don't have abbl BCR Fusion the patients with CML have it how many of you got it that will lead to abnormal tyrosine kindness and that will lead to uncontrolled mitosis now what if I want to treat this patient let me tell you the treatment here only I want to treat this patient so basically I will give targeted therapy the name of that targeted therapy is tinib have you heard the name imitan imitan have a special role because it is the first targeted therapy in the discovered in the world there are many targeted therapies now available for the cancers but it is one of the first you know it is the first targeted therapy which was discovered okay so tin is the name of the drug the most important thing is the oral tablet it is available in oral form so patient has to take one tablet daily patient don't have to hospitalize go to the hospital and take long chemotherapy no no it's the chemotherapy only but the patient will take in the form of the tablet easy to take the root of administration is easy so patient has to take one tablet daily okay and what does the imip will do imip will do the apoptosis of all those cells in the bone marrow which is having this Fusion Gene all those cells will undergo apoptosis apoptosis and imit will inhibit the abnormal tyosin kinosis so imip will control CML after the discovery of imit inip the prognosis of CML is very good very good hardly any patient have any adverse effect or any poor prognosis okay because of the discovery of tinib before that we used to do bone marrow transplant and other chemotherapy drugs that is not very successful but tinib is a real game changer in case of CML are you getting it are you getting it say yes or say no say something but respond people respond it's a live session keep interacting got it got it can we go ahead so this is the complete story for CML so tell me what is happening say ma'am we understood this master diagram now in this diagram only I will teach you four leukemias please understand I taught you the first one the pathogenesis of the first one you tell me what is happening in the first one say ma'am in these five cells can you enumerate the five cells say ma'am myoblast prosite myosite metam myosite and B form in these five cells 922 translocation is taking place 922 we write it like this 9 semicolon 22 and we make a small bracket and we write down a small T it's a conventional we write like this only it means that there is the exchange between 9 and 22 so that is a translocation balance translocation or instead of that you can write down the name of the gene itself on nine is the number of the chromosome 20 is the number of chromosome on them name the gene so you can say albl BCR translocation it is also good to say Al BCR one and the same thing whether you say 922 or whether you say abbl BCR the meaning is the same got it so basically in these five cells this is happening 922 translocation or AB BCR translocation because of that they all five are doing uncontrolled mitosis because abnormal tyrosine Kus is formed in all five so these five are doing uncontrolled mitosis because of the uncontrolled mitosis these five are spilled in the blood so these five are coming in the blood so myoblast in the blood what what is coming myoblast prosite myosite metam myosite and band forms along with a little bit mature form neutrophil eosinophil basophil and monoy but they are very less maximum of them are immature form so if you take the blood sample of this patient in a test tube what do you find what do you find you will find maximum at WBC WBC are nearly two lakh or three lakh but you see they are not the mature one maximum of them are immature ones maximum of them are immature ones how many of you got it so what is the um what is the uh function of WBC why God has provided us with WBC see WBC does the defense they are like Army the God has provided us the army so you may be thinking normally how much Army I'm having I'm having 4,000 to 11,000 soldiers in my Army how many soldiers I'm having an adult human being healthy human being have 4,000 to 11,000 soldiers in the Army here the person is having two L soldiers in the Army youum the person will be super immune no no no these are these are immature ones these are not mature soldiers these are not mature forms these are immature ones so person is prone to infection you see ma'am the two things are contradictory yes it is a paradox although the person is having high WBC count still the person is having high susceptibility of infection you will see how how the two things together you are saying High WC count still person is high suceptibility of infection yes the answer is immaturities they are high but they are immature they don't do their function properly so that's why the person is having high susceptibility of infection all Leukemia patients have high susceptibility of infections got it soon I will cover MPN and MDS also aush definitely I will cover one by one we will cover okay can we go ahead how many of you got it okay so the same thing is shown to you normally a is present on n and BCR Gene is present on 22 okay let me show you this side concentrate on this side this is normal don't see the translocation right now see the uh left hand side first see this is a pair of nine you can see the two chromosome and this is a pair of 22 see the two chromosome I want to highlight the one one gene on each of them I want to highlight nine have a concentrate and 22 have BCR so it's normal they are doing their responsibility normally they are doing their function normally abl on 9 BCR on 22 everything was good to go everything was good to go but now because of translocation you can see what is happening see 9 a is going on 22 on which BCR is already there now you can see on the 22 what is happening on the 22 there's a fusion genus formed can you appreciate the fusion gene or hybrid Gene because BCR was already there and a is also coming and this is deadly that will lead to uncontrolled mitosis in exchange of that the 22 is giving a portion to nine that don't contain any important gen so this is translocation how many of you got it how many of you got it so what is happening in translocation so if you're going to write in your exam now like if you have Theory exam write down in the form of the project and if you have to solve McQ it will be easy to solve now Al is present on nine normally it got translocated to 22 on 22 we already have BCR so Al BCR hybrid Gene is formed that is known as Philadelphia chromosome so 22 is Philadelphia not 9 it's a very important McQ it's a very important McQ and that that will lead to abnormal tyrosine kindness that will lead to uncontrolled mitosis and that will lead to CML so this is the complete story of CML okay so in CML all these cells are doing uncontrolled mitosis and because they are doing uncontrolled the five cells Milo blast Troy miloy metam myosite and B they doing uncont controll matosis so they are replacing everything else in the marrow everything else in the marrow they are replacing once the marrow is full full full they are spilled in the blood they are spilled I'm using the word spill spage they are spillage they are spilled in the blood so In The Blood also you get all five you will get you will get myoblast prosite miloy metam myoy band form and along with the few mature versions neutrophil eosinophil basophil and monoy you will get all this on the blood all this in the blood so if you make a slide if you take a slide and make a smear if you make a smear of the blood sample here if you make a peripheral smear you will get all these cells you will get all these cells it is typically known as Garden Party Garden Garden Party have you ever visited a garden party Garden Party everyone is in a different dress it's not school uniform in school uniform everyone is in a same uniform the same dress the same dress code in a garden party everyone is in different beautiful dresses so you getting different type of s so this typical appearance of CML is known as Garden Party appearance it's a way to remember it's a way to learn okay uh sa I'm coming on this 210 kilon intentionally I have skipped it let me tell you when I will teach you the AML I will teach you this because in AML also there will be 922 translocation but the size of that Fusion Gene will be different there it will be 180 here it is 210 I will help you learning there okay got it can we go ahead if you got it okay so as I told you all these cells are coming in blood but the most important is blast which blast myo blast based on the blast there are three phases in CML there can be chronic phase accelerated phase or blast pH you can learn the pneumonic cab chronic accelerated blast cab cab there is chronic iic phase there is accelerated phase and there is blast phase so how much myoblast if myoblast is 10 less than 10% it's chronic 10 to 20% it's accelerated and more than 20 it's blast phase so in Blast phase patient is highly symptomatic how many of you got it so B based on that we give the uh based on the blast percentage we give the phase in which phase of uh CML uh the patient is it is a triphasic leukemia we can see it's it's a leukemia which is triphasic so that is the pathogenesis how many of you got it give me a thumbs up if you got the pathogenesis what is happening everyone got it what is exactly happening in the CML CML is a leukemia so CML is a blood cancer the people the students the audience who can understand this master diagram can understand everything so that start from the basic if you have missed the initial of this lecture now please go and First Watch the initial lecture first understand how the doues are formed got it then only you can understand this so basically in CML the precursors of the myoid series that is these five precursors they have mutation in them so name the mutation simam 922 translocation or abl BCR translocation because of this translocation they become cancerous cell and they are doing uncontrolled mitosis and they all are spilled in the blood so in the blood all five are present and that is CML we got the pathogenesis with this pathogenesis coming on the clinical feature now clinical feature are due to bone marrow failure I'm seeing now you understand this diagram also I have explained you at the beginning of the lecture in the bone marrow rbcs are also formed platelet are also formed and you know myoblast is also formed from the common myoid progator common myoid progator RBC WBC plate they all are forming now I'm saying there is mutation in the myoplast so Milo blast and their their precursors are doing uncontrolled mitosis so they replace everything else they replace everything else they replace the RBC also RBC and their precursor also arthid precursor and they replace the platelet or Mega caride precursors also so patient have anemia because RB are not formed patient have thrombocytopenia because platelets are not formed because it is replaced by the myoblast myoblast and the precursors the five cells which five cells myoblast prosite miloy metam myosite and Bank bom they are doing uncontrolled mitell so the complete marrow is filled with these five cells and all other cells are replaced so no rbcs are formed or very few rbcs are formed no platelet are formed or very P plated so patient have anemia so patient will come to your doctor I'm have lethargy parar fatig you know lack of energy disia because of the anemia patient have multiple bleeding disorders like patient have bruises py bleeding from the gums bleeding from the nose epistaxis bleeding from the ears or internal bleedings like so because of thrombocytopenia okay and you will say wbcs are too high but still patient is highly prone to infection because I agree wbcs are too high instead of 11,000 they are two three lakhs I agree I totally agree but they are immature so they will not do their function so person is having anemia bleeding disorder and infection so technically the person is presenting like pancytopenia although rbcs are less okay platelet are also less okay but WBC are not less in panopia W WBC are too high here so because RVs are less patient have anemia because plat late are less patient have thrombocytopenia bleeding disorders but WBC are high still patient have high propensity or susceptibility for in AC action because of the immature forms okay apart from that there is hyper metabolism the cells are formed more they are they are like you know they will be dead more so there is weight loss night sweats anorex and spomal masses all these cells will go the immature cells which are there in the marrow uh they are spilled in the blood they will go in the screen then they are trapped in the screen so patient present with the massive Spen you got my point so this is a blood vessel okay this is a blood vessel in the blood vessel normally 4,000 to 11,000 WBS are present but now there are two lak wbcs are present so via blood they all will be moving to the spleen and they are trapped in the Spen and that's why the Spen will be enlarged and that is spomal this is the reason for hypers spomal so please understand everything don't mug up please understand everything now coming on the lab diagnosis of CML in the lab diagnosis not only of CML of all leukemias there is a fixed format so I will tell you the lab diagnosis in these headings only first tell me what will be the change take the blood sample of the patient aspirate the marrow take the bone marrow biopsy as well as bone marrow aspirate do the cytogenetics by doing kot typing okay do the cytochemistry that is the special stain special stain cytochemistry means special stain cytogenetics means kot typing you are doing the kot typing the genetics the molecular studies and others are not important so blood blood study bone marrow study genetic study and special stain by these four things we will do the diagnosis of all leukemias how many of you got it how many of you got it okay so in the blood will see three things what happened to hemoglobin obviously hemoglobin will be less because rbcs are less because the rbcs and plat lates are replaced by the immature wbcs so that's why less hemoglobin less plat late but WBC will be too high H know so patient have anemia rbcs are less hemoglobin is less patient have thrombocytopenia the plat lates are less patient have bleeding and wbcs are nearly two lakh instead of 11,000 it's 2 lak but but but add a but here they all are immature forms you can see the diagram see see the diagram how many type of cells you can see in this diagram I can appreciate this is a eopl because it is having red granules this is a basophil because it is having the bluish granules and this is the neutrophil the adult the mature neutrophil I can see the multilobated nucleus with the pink pink granules this is a band form this is a prosite this is a metam myoy likewise so I'm getting a abundant of cells H know so I'm getting all these five cells in the blood along with the neutrophil EOP basophil so this is the diagram you can see this one you can see this one so I appreciate you are getting bopy you are getting eosinophil you are getting neutrophil you are getting all other cells also the band forms are usually you can identify they are c-shaped the nucleus is c-shaped the c-shaped are the band forms you can see these all so you can how many cells you can see say ma'am I can see prosite mosite metam myosite band form basophil neutrophil eosinophil and the myoblast the most important you get the M blast this is known as Garden Party appearance what is it known as people it is known as Garden Party what do you mean by garden party in garden party everyone is in different dra so Garden Party appearance typical appearance of CML never forget so out of the four leukemias I have finished one I have completed one three more to go in the end you can understand the paral mirr of all four but currently let's have a look of CML in the CML appreciate the word ma'am there are four type five type of cells Milo blast prosite miloy metam miloy band form along with neutrophil EOP and basophil and monocytes so this is Garden Party appearance and you can appreciate it in the diagram now you will appreciate once I will cover all four and you can make out the differences okay currently CML is done so blood picture I told you the WBC peripheral smear also we have seen now coming on the bone marrow in the bone marrow tell me the cellularity the cellularity I told you what is happening in the bone marrow in the bone marrow the Milo blast is doing control mitosis so obviously cellularity is more as compared to a healthy individual the mil the myoid cells will be more the other cells are not more so erythroid cells are less Mega Cario sites are less and overall myoid cells are more out of the three myoid are abundant iiid and megao alness so that is the bone marrow obviously you can understand it so we have seen the blood picture we have seen the bone marrow picture now see the genetics if you see the genetics you will typically get 922 translocation you will get it and this is a confirmatory diagnosis but it's very expensive but if it is done it is confirmatory diagnosis so we can confirm it via cytogenetic stereotyping 922 translocation cytochemistry is a special stain it's a type of stain it's a special stain it's a special stain okay what is the special stain here we use the name of the stain is neutr alkaline phosphatase nap or also known as neutr is a type of lucite no lucite is WBC it is known as lucite alkaline phosphate is lap so whether you say nap or whether you say lap the meaning is the same what do you mean by nap or lap neutr alkaline phosphatase or neutral is a type of lucite only lucite is wz there are five type of wz so lucite alkaline phosphat you say what does it mean what does it mean it it is a stain that will highlight the granules the granules you tell me you tell me this is the complete series okay the these are this is neutrophil you know neutrophils have granules in the cytoplasm yes or no so but but it precursors don't have granules granule formation start from prosite and myosite and they have less granule gradually it increase increase and maximum granules are present in neutr maximum granules are present in neutrophil the precursors have less granule so I'm saying that in CML the precursors are coming more in the blood I know the precursors are more the myoblast prosite miloy metam myosite and band form are coming more in the blood as compared to adult neutr ad nrop is there but it's less so you tell me what happens to the nap score nap score in CML nap score will be more as compared to normal or less as compared to normal normally the nap score is due to adult neutr here adult neutrophils are less so nap score will be less because the granules are less the precursor don't have granules so nap score will be less so in CML the nap score is less not more so please learn the nap score here what is nap score the nap score in CML the nap score is reduced how many of you got it how many of you got it okay say yes if you got it so this is the reason why the nap or the students learn it but they don't understand why the Napper laap score is reduced in CML it is not increased highlight it is reduced in CML now the most important differential diagnosis of CML we are done with the diagnosis okay we we have seen the blood picture bone marrow picture cytogenetics and cytochemistry here the nap score is reduced we have seen That Others May uric acid will be high because there are most more and more cell they are form forming and more and more cell are dying also whenever cell is birth they are dying the uric acid will be more so patient presents with gout or hyperemia we got it so this is the complete diagnosis now coming on differential diagnosis of CML in CML the most important differential diagnosis is leukemoid reaction what do you mean by liuk reaction leide reaction is a condition in which if you check the WBC count in the blood it is nearly 50,000 to 1 lakh it is not more than 1 lakh never it is 50,000 to 1 lakh okay normally it is up to 11,000 but it's not cancel it's not lukemia so sometime you can get confused is it CML or is it simple lukid reaction lukid reaction is not cancer you know so whenever you know there is a human being this is the blood vessel of the human being in the blood vessel wbcs are there these are the wbcs normal count I told you is 4,000 to 11,000 okay now whenever any infectious organism like the bacteria virus fungus parasite or any malignant cells or anything any foreign particle okay it is entering in the blood what happens this is the Army now they will increase they will increase so instead of 4,000 to 11,000 they will increase increase increase increase and they will become nearly 50,000 so it's reactive it is reacting in respond to exogenous agents okay it's not cancer here mutation doesn't happen it is leukemoid reaction lukid reaction happens in response to inection in respond to infection sometimes the WBC count is too high but it's never more than 1 lakh it will be nearly 50,000 maximum up to 1 lakh but never more than 1 lakh it will never cross one lakh in cmn it is 2 lakh three lakh like that how many many of you got it this one is reactive that is licom reaction it is excessive lucyisanerd that resemble CML but the patient don't have CML so don't start emit here being a doctor don't get confused that you are doing the CBC in the CBC you got a WBC count as too high it is nearly 50,000 60,000 or one lakh and you cannot make the diagnosis oh my God CML start a no no no first do the cytogenetics confirm is it 922 translocation yes or no mutation is there yes or no then only you start the treatment otherwise don't start it can be lukid reaction so sometime you can get confused the blood picture is same as that of CML but here hipat pom these all are absent got my point and there is no bleeding disorder patient don't have any anemia other other things are absent it happens in response to infections or sometime in response to toxins and rarely in certain malignancies so that is known as Li reaction you will say ma'am how I differentiate being a doctor for example a patient is coming to me of the age of the patient is 50 years and patient is complaining that I'm having very frequent infection okay and I have done a CBC for certain disorder I I have done a CBC in the CBC I found the WBC count is nearly 1 lakh or 50,000 H so I can get confused ma'am is it liimo reaction so I will not start the chemotherapy or is it CML I will start so how should I differentiate based on the peripheral smar based on peripheral smar how cytogenetics definitely you can differentiate but based on based on peripheral smar how do you differentiate so listen so here the lab findings it it will never exceed one lak I told you in licite reaction it will never exceed one lakh and in CML it is more than one lakh okay see see the differences here let me tell you in leukemoid reaction versus CML you get many questions here luide reaction versus CML in leide reaction the count is 25,000 to 1 lakh normal it is 4,000 to 11,000 never forget in CML it is more than one lakh nearly 2 lakh three lakh like that here you will get predominantly neutrophils the mature neutrophils here you will get all mature stages here you get only neutral here you will get prosite myosite metam myosite band form along with neutr not only neutrophil here basically you will get neutr okay here nap score is more here nap score is less because nap score will highlight the neutral I'm seeing here neutral is more and I'm seeing here neutral is less so nap score is something that differentiate the two and you get many mcqs on Nap score so that is the significance of the nap score if you do the fil chromosome obviously it's absent here here there is no no mutation here Philadelphia is always present if you do the ab BCR Fusion Gene it's absent here it's present here got my point here organ infiltration is absent here also absent but sometime may be present here spomal is absent here it's present I told you the reason for the spom also got my point how many of you got it how many of you got it we are done with CML finally the treatment I told you the treatment is imit imip the most important therapy for CML is imip and you can do for anemia you can give the symptomatic treatment like blood transfusion for thrombocytopenia the symptomatic treatment is PL transfusion before emit we used to do bone marrow transplant but nowadays we don't you do bone marrow transplant because imit is available we hardly or barely do it how many of you got it how many of you got it huh and finally the prognostic factors I'm coming on your doubts wait so finally coming on the prognostic factors of CML we have two index soal index and has four index to see the prognosis in them the four four things are common don't learn them the fifth criteria is different here we see the cytogenetics here we see the bases basically you don't get any much mcqs on the prognosis of CML but you have to read it the two type of the systems we are done how many of you got it I'm done with CML I taught you everything about CML in the similarly way we are going to cover AML Al and cl right now now the remaining three will be little bit faster because you already have a idea now this was the first one now it took time I agree it took time but it was worth giving the time because the remaining three will be really very fast how many of you got it huh so the nap or the lap score okay listen tell me the precursors who's asking tell me the precursors someone is asking to repeat the nap score or the lap score say the full form what is nap score or lap score it is neutrophil alkaline phosphates and neutrophil is one of the lucite only now so also known as lucite alkaline phosphates so basically tell me the precursors we have hematop stem cells it give rise to myoblast prosite oite metam myosite band form and finally neutrophil let me draw these cells to explain so this is a cell of myoblast this is prosite then myosite then metam myosite band form is c-shaped and finally neutrophil is multilobed like this now let me draw the granules inside them I'm interested in granules basically to explain you the Naps code so maximum granules are present in the neutrophil a little bit in the band form very little in the mat metam myosite and hardly no granules here granules so nap or lap score is something it is neutrophile alkaline so it is a alkaline phosphates alkaline phosphates is a component of granul so you tell me which cell it will stain it will stain this cell maximum a little bit of this a little bit of c and it will not stain these one now you tell me what is happening in the lukid reaction in lukid reaction neutrophils are increasing in the blood up to one lakh not more than that so lap score will be high what is happening in CML in CML these cells are increasing not the neutrophil so their nap score is less so in C ml the na score is less and in leukemoid it is more who was asking give me a thumbs up you got it or you didn't got it the concept should be crystal clear to you got it I will cover all the topics I will cover autocoids also okay okay definitely I will cover the anticancer pharmacology also Muhammad okay what else so whatever topics you want now write down in the chat I'm having a eye there and definitely I will schedule them one by one okay so there's a fixed schedule protocol in which we are going to schedule all these sessions one by one based on the demands of the student so the student which who are demanding a topic more we are scheduling that prior but definitely we are going to schedule all of them one by one everyone got it can we go ahead can we go ahead let's solve some mcqs on CML and come on the next leukemia so the first question is in front of you write down your answer in the chat box right now read the question and tell me the answer quick fast Sho quick fast tell me the answer H what causes this pom I already told you aush listen so this is the blood vessel in the blood normal count of WBC is 4,000 to 11,000 but in CML instead of 4,000 to 11,000 it is 2 lakh so imagine 2 LS WCS are there they all will move to the spleen they will move to the spleen and spleen will trap them because High cells are there and spleen will enlarge so massive Spen this is a reason I hope you got it read the question tell me the answer a uh BCR abl hybrid Gene is present in which leukemia obviously the question is very easy is it burket lymphoma retinoblastoma breast cancer or CML I the question is super simple of course the answer is CML so I'm not waiting I guess everyone yes yes correct answer is D and you all are right you can see abl BCR Fusion on the Philadelphia 22 chromosome read the next question it's a clinical case so we will read it understand it and then come on the answer listen listen there is a 60 year old man age is always important people age is always important 60 year old okay there is an old man presented with fatigue fatigue means patient have anemia weight loss weight loss means patient have hyper metabolic and uh the hemoglobin is 10 so of course the patient is anemic the WBC count is 5 lakh oh come on 5 lak normal is 11,000 it's 5 lakh so definitely it's a case of leukemia platelet count is 4 lakh which is normal 1.5 to 4 lakh is normal okay now coming on the DLC in the DLC neutrals are 55% lymphocytes are 4% monoy are 2% Bops are 6% which is more but there is metam myosite myosite prosite and blasto normally they are not present in blood so of course it's a typical case of CML and if it is CML what is the correct answer you can read the four mutations of course in CML the most important mutation the only mutation is 922 translocation that is Philadelphia chromosome So based on that first make the diagnosis of CML and based on that come on the transportation I hope you all are right the correct answer is 922 this is the clinical scenario and this is the approach for that okay now coming on the next question easy question chromosomal translocation in CML I guess everyone know is it 28 814 922 or 1570 what is the correct answer of course the correct answer is 922 we have seen here 922 if I change from CML to AML answer will become D I will tell you in AML also especially AML and three type I will come on that okay now coming on the next question a parital smear is having neutral neutral we all have there is nothing important in that basl we all have that usop we all have that but we don't have myoblast prosite and band form in the peripheral smar we have these cells in our bone marrow but if you check my peripheral SM I don't have it okay so if these are present in the blood what does it mean is it mean AML Al CML or MDS what does it mean of course it is a garden party appearance multiple type of cells and Par mirr it is known as CML the correct answer is C and you all are right you all are right absolutely right absolutely right okay so let's move ahead CML is characterized by all except what do not happen in CML tell me Lucy Tois yes or no lucis yes or no lucis means increased WBC count yes if the WBC count is 2 lakh three lakh four lakh yes trombocytopenia yes the plate plate will fall this is also right spom yes spom also occur but is it increase lap or increase nap no no no no no lap or nap is decreased not increased increased lap or nap occurs in lukid reaction not in CML so correct answer here is C because it doesn't happen they are asking accept you can see the lap or the nap score is something that differentiate the lukid reaction from CM you have to learn that okay you have to learn that tell me the next thing the difference between leukemia and leukemoid reaction is done by what I want to differentiate the CML from the leukemoid reaction how to differentiate is it lucos alkaline phosphites is it immature self is it total count or is it ESR total WBC count is raised in both of them ESR we can't do ESR based on ESR we can immature self basically immature self are more common in leukemia but sometimes they present in leukemoid reaction also so the best to differentiate is the lab score lab score is high in leukemoid reaction and lab score are low in CML so lab scores are important so we are done with CML I hope you know the definition age mutation the three phases clinical feature lab diagnosis treatment and prognosis of the CMS can I skip and come on the next one EML can I start the EML give me a thumbs up Are you full of energy still H can we continue the next leukemias with the same energy with the same enthusiasm yes give me a thumbs up let's start AML so coming on the next one AML okay so let's start the next one AML acute myoid lukemia AML so what is happening here listen listen people come here the first thing look at the age the CML was occurring after 50 years usually exceptions are always there AML usually occur 15 to 40 years not in old age AML do not occur in old age us usually but exceptions are there I told you exceptions are there okay got it so here usually we get the AML between 15 to 40 years now see that what is the difference in pathogenesis everyone on the screen what was happening in CML see m in CML these five cells have the mutation which mutation it was 922 translocation because of which these five were moving in the blood so in the blood we were having all five myoblast prosite myosite metam myosite and band form including blast also but all five are there and the neutrophil EOP basophil monoy they all are there they all are present here got it say yes or no so they all are present in the blood that is Garden Party appearance okay that was CML CML what is happening in AML mutation occurs only only in myo blast that's it that's it none other cell b mutation I will tell you mutation will be different there are different type of AML in which different type of mutations are there here the translocation is 15 17 either 1517 or translocation between 821 not 9:22 or there is inversion 16 the 16 there is a gene in the 16 which get splitted and inverted so inversion 16 inversion 16 so either 15 17 821 or inversion 16 one of the mutation usually occurs here only in myoblast so in the blood only myoblast is coming not this only myoblast is coming so school uniform appearance that is AML how many of you got it how many of you got it say yes if you got it H so in AML only myoblast is mutated and that is doing uncontrolled mitosis so that is filling the Maro compet and spilled over in the blood so here if you take the blood sample and make a smear in the smear you will get only one type of cell that is Mito blast there are eight type of AML based on fat classification we don't have fat classification for CML in the CML we were having three phases chronic phase accelerated phase and blast phase if you remember here we don't have phases we have fat classification the French American British classification based on which there are eight type including m0 so m0 M1 M2 M3 M4 M5 M6 M7 there are eight type of EML you have to learn their names sometime you will get the names in the options so you don't recognize is it M1 M2 M3 so you have to understand that m0 is minimally differentiated AML minimally differentiated AML M1 is AML without maturation M2 is AML with maturation learn these three minimally differentiated without maturation with maturation now after that I'm having a way to learn that M3 is Pro prootic leukemia prootic this is Milo just a second this is learned as PM prootic this is Milo monocytic and this is monocytic this is arthrotic and this is Mega carotic let me tell let me tell you so we are having totally eight type m0 M1 M2 M3 M4 M5 m6 and M7 how to learn that so AML with minimal differentiation minimal differentiation without maturation with maturation we have learned these okay now how to learn M3 is prootic acute prootic leukemia M4 is milom monocytic this was prootic this is myom monocytic acute milom montic lukemia M5 is monotic only monotic so acute monotic leucemia then M6 is arthrotic acute arthrotic glucemia and M7 is meiotic so acute Mega Leia how many of you got it so you can read the word prootic milom monocytic monocytic arthrotic and meiotic leucemia acute in lukemia you can add anytime say yes out of which there is a special type that is M3 in M3 there is always DIC disseminated intravascular coagulation DIC is there okay so I will tell you the special special points in all seven all eight one by one uh all of them are M positive m is a special stain I will tell you what is M but here this one is M negative only this is MP negative rest all are M positive what is M I will tell you later it is it's a type of special stain okay Milo peroxidase Milo peroxid stain is there okay M1 nothing important M2 in M2 there is 821 translocation and maximum chances of chloroma I will tell you what is chloroma okay in M3 1517 translocation is there and maximum I rods are seen in M3 and in M3 di is also there in M4 inversion 16 translocation is there in M59 11 translocation is there so something something special in each of them out of them the least common type is M7 and the most common type is M2 so you have to learn these special Point most common type is M2 and least common type and the worst prognosis of all is M7 M7 is the worst one okay and it is present in Down syndrome the M7 so you get simple simple mcqs on that now what are the clinical features of course in all Leukemia all full leukemia these three clinical features are common now here the Milo blast is doing uncontrolled mitosis so it replaces RBC RBS are not formed it replaces plate plate are not formed so since RBS is not formed patient have anemia since plate is not formed patient have reading disorders of thrombocytopenia and since myoblast are present in the blood you know the mature forms are not coming only myoblast are coming in the blood that's why patient have high propensity of infection also so these are the clinical features you will say this is common as it of CML in CML also we have this okay I got it but there is one additional feature which was not present in CML everyone here listen let me tell you one difference between CML and AML you tell me what is the difference what was happening in CML please understand what was happening in CML all these five cells were doing uncontrolled mitosis because of 922 translocation and they were shifted in the blood and after coming in the blood these all five they remain in the blood only they remain in the blood only they don't go anywhere else organ infiltration is not there in CML now please understand what is happening in AML please understand here what is happening in AML in AML only Milo blast is doing control mitosis and only myoblast is coming in the blood others are not coming okay school uniform appearance and after coming in the blood it infiltrate in various solid organs and producing lymphomas so lymphoma is a feature of AML it's a feature of AML but not CML how many of you got this point how many of you got this point organ infiltration it is known as organ infiltration so organ infiltration occurs in AML myoblast do so but in CML it doesn't occur it never occur say yes if you got it how many of you got it huh got my point so in which organ it is infiltrating enumerate them it can infiltrate in the bone so patient have bone pain it can infiltrate in the lymph node patient have lymph node lymphoadenopathy lymph nodes are enlarged it can infiltrate in the Spen spom in the liver hipat in the kidney kidney infiltrates are there it can infiltrate in the gums also can you see gum hypertrophy the blast Milo Blast from the blood they are moving in the gum and dis producing the gum hypertrophy which is very peculiar it is seen in M4 and M5 M4 and M5 you get the McQ on that not in others M4 and M5 and it can move in the orbit and it can swell the eyeball orbit orbit okay it is known as chloroma it is known as chloroma in the eyeball it is known as chloroma and it happens in M2 so chloroma happens in M2 and the gum chloroma in the M2 and this one in M4 M5 M2 M4 M5 M2 M4 M5 in the orbit it's chloroma here it's M2 and in the gum it's M4 M5 how many of you got it say yes so this is the organ infiltration which is not a feature of CML but a feature of AML coming on the lab diagnosis quickly in the lab diagnosis of course in the blood hemoglobin is less plate is less and WBC will be more of course hemoglobin will be less plate will be less WBC will be more it is more than one lakh but only one type of cells in CML we got these five type of cells in the blood no not here here we get only one type of cell which one myoblast that's only one cell myoblast so only myoblast is coming in the blood and 99% of the cells in the blood are myoblast no other cell it is spilled over because of the UN because there are mutations here either 15 17 mutation or 821 mutation or inversion 16 mutation because of which it is doing uncontrolled mitosis and it is spilled in the blood once it is coming in the blood it is spilled in the blood so you will get only one type of cell myoblast can you see only one type of cell now see this picture which how many type of cells I get only one type of cell these all cells are myoblast you can see all the cells shown in this image they all are Milo is not Garden Party appearance you will see it's a school uniform appearance the in a school uniform everyone is in the same dress so you can see uh in the cytoplasm the red color rods are present in the cytoplasm these are Aur rods based on the Aur rods if you attending my lecture from the beginning you understand I can identify this is myoblast not lymphoblast because I rods are present so I Rod is a feature that differentiate the myoblast from the lymphoblast yes IOD is the feature okay here iods are present maximum iods are present in M3 now you can understand all those maximum iods are present in M3 it is present in M3 maximum iods so it is not present in all myoblast you can see out of the seven eight cells shown to you only three of them have IOD this one this one and this one others do not have so a myoblast this is a myoblast this is the nucleus of the myoblast a myoblast which is having iods in the cytoplasm such a myoblast is known as fot cell what is cell it's a myoblast with iron so maximum fot cells are present in M3 or maximum IOD cells are present in M3 it's a question it's a McQ please learn that got it so out of the four to you can understand now I want you to compare the AML with CML compare these then we will come on the leukemoid first see the myoid liukas we are done with the myoid leukemias by the way so please can you compare no say ma'am here in AML only myoblast are present in the blood I can see only one cell and in CML I can get myoblast but along with myoblast I get prosite myosite metam myosite band form neutr eosinophil basophil monoy everything so here it's a garden party appearance and here it's a school uniform appearance you can compare don't mug up I want you to have a look on this peripheral smear and on this peripheral smear see how many type of cells you can see here and see only one type of cell here that to with the aod so if the peripheral smear is provided to you in your exam can you identify which type of lukemia is it say yes if you got it say yes huh what's the purpose of M1 M2 M3 uh C suria so at your level if you're doing mvbs now so learning the classification is only important but the prognosis of all of them is different the mutation of all of them is different the treatment of all of them is different so if you are doing your MD in hematology or in pathology then understanding the various types with their prognosis with their treatment form will be important for you but now at your level generalized learning the classification is more than sufficient but these are different eight types having different treatment and different prognosis got my point so treatment will be different prognosis that is the only answer can we go ahead H yes got it so we have seen the blood picture now coming on the bone marrow of course cellular is more in the bone marrow you can see hyper cellular because myoblast are doing uncontrolled mitosis and replacing everyone so here most of the cells are myoblast milod are more than 20% usually it is less than 5% here more than 20% and they have iods in them they are fot cells IDs are less and mega carite are less so obviously we can understand okay obviously we can understand now cytogenetics you will get the three type of mutation in M2 it's 821 translocation in M3 it's 1517 and in M4 it's inversion but in others there are other translocation don't learn them usually you get cion on these just a second give me a minute just a second give me a minute let me share it again okay I guess you can see okay so please learn that in M2 in M3 and in M4 so in M2 it's 821 in M3 it's 1517 in M4 it's iners 16 on which you get the question inside chemistry listen I am teaching you four types of leukemia this is the second one we have already completed CML yes or no we have already completed CML yes now after that I am covering right now AML after that I will come on a also okay and finally I will come on CL so basically the cytochemistry the special stains are important here here here here we don't have any special stain okay so here in CML I told you only one special stain to learn nap or lap score nap or lap score and that two falling in CML this is required to differentiate the CML from liid reaction we have seen that now basically the real confusion occurs here and here here H here also school uniform appearance here also school uniform appearance here in the blood you get only one cell myoblast here in the cell you get only one cell that is lymo blast here the mutation occur in myoblast that is doing uncontrolled mitosis and Spilled in the blood here the mutation occur in the lymphoblast doing uncontrolled mitosis and Spilled in the blood the only way to differentiate them is IOD here IOD is present here IOD is absent but sometime we cannot appreciate the IOD and we really get confused that which type of leukemia is there so clinically both of them are same okay this is also acute this is also acute acute must have bad poor prosis how many of you get it so here really we want the uh cytochemistry so I will tell you total five STS three of them are positive here but negative there and two of them are positive here but negative there so learn the total five together at one shot at one place at one shot to differentiate the two acute glucas from each other okay so these are the five special stains out of the five mpo Sudan black and nsec is positive in AML but past and acid phosph is negative here in AML pass and asset f is is positive in Al but not in AML you are getting my point you getting my point so the three so you can compare the AML with the same table I will show you in the next leukemia when currently I'm teaching you AML after this I will teach you Al so cytochemistry I'm teaching you in common for both of them so learn the five stains mpo myop peroxidase it is positive here there are eight types it is negative in m0 and except m0 it is positive everywhere for from M1 to M7 but it is negative in m0 and here it is always negative it is always negative Sudan black it is positive in AML but it is negative in Al NST NSE is non-specific hisory please learn n it is also positive only in M3 M4 M5 not others only in M3 M4 M5 but it is always negative here the pass passes periodic acid shift it is positive there and acid phosphorus is also positive there so these are the two which are positive there and these are the three which are positive here how many of you got it so mpo Sudan black NSC pass acid posties so learn them in a sequence and learn a ml a ll I want you to learn these three are positive here but negative here and these two are positive here negative here this is a generalized thing but here m is positive everywhere except m0 you have to learn that H and NS is positive only in M M3 M4 M5 not everywhere M3 M4 M5 yes so how many of you got it give me a thumbs up H give me a thumbs up you got it so please learn that so can we go ahead can we go ahead so that is the cyto chemistry others not important we are done with that and the treatment here we don't have any targeted therapy unfortunately we have targeted therapy for CML the CML targeted therapy is imitable here we have to perform bone merot transplant if donor is available if the age of the patient is young donor is available a chil matching is there and everything is suitable the best is go to with the bone marot transplant if bone marrow transplant is not possible we will give the chemotherapy we don't have targeted therapy which chemotherapy we use three drugs we use cytosin arabinoside anthy and six thin we use these three the combination of these three chemotherapy we don't have targeted therapy this we will give everywhere except M3 in M3 we give retinoic acid treatent toin as a treatment because in M3 we have DIC in M3 we have DIC please learn M3 is a special type what are the eight typ types I told you m0 M1 M2 M3 M4 M5 M6 M7 can you tell me the important features of all of them m0 learn it is M negative rest all are M positive M1 M2 nothing important nothing important M3 me DIC it is a unique having DIC here maximum fot cells cells maximum Aur rods maximum iods maximum fotel okay and um in M2 chloromas are there in M2 chloromas you know what is chloroma orbit get swelled chloromas are there and in M4 M5 gum infiltration is there gum infiltration is there these are the important points you have to learn it I've told you already we are revising and in M3 M4 M5 NSC is positive that's it so please learn it is already given in the notes please learn that these are the important points the most important is DIC so for that the treatment of all of them is same we give chemotherapy you know the three chemotherapy drugs but treatment of M3 is different we don't give chemotherapy here we give retinoic acid or trenin here got it so please learn now coming lastly on the prognostic factor you get many questions on the prognosis of the AML please learn that so learn the good prognostic factors and bad prognostic factor most important is the age if the age is less than 40 prognosis is good if age is extremes either less than two or more than 50 55 the prognosis is poor so extremes are poor the middle AG is good but extremes are poor M2 M3 M4 is good but except that m0 M6 M7 are poor okay M1 is moderate you can say okay so M2 M3 M4 are good you have to learn that blast with Aur Rod this is the kot type is good but complex kot type is bad if total lucite is less than 2.5 lakh is good if it is more than uh you know uh less than I'm sorry 25,000 is good if more than one lak it's bad uh 15 17 8 21 and inversion 16 is good but apart from that deletion of five deletion of seven is bad these three the which we have learned these are the good so you have to learn the good and the bad prognostic factors we will solve some mcqs and we are done with AML also so out of the four two are done how many of you got it read it all of the following are poor prognostic factors except which of the following is not a poor prognostic factor in AML is it inversion 16 good or bad I guess this one is good this one is good complex kot type it's bad M7 it's bad and dele uh 7 Q it's bad so only one is good that is inversion 16 rather than Anna don't judge don't guess I mean have a look on this table and then tell me so you can see inversion 16 is coming on this side but the remaining three are coming on that side you can see complex kot type you can see M7 type and you can see delution of 7 Q they are the bad ones so basically you have to learn the prognostic factors please I'm insisting please yes you all are right absolutely right okay the next one AML with gum infiltration hipat Mig most likely to be so gum infiltration occurs in which one I told you gum infiltration chloromas occur in M2 but gum infiltration occurs in M4 and M5 out of M4 and M5 only M4 is given in the options so go with M4 if M5 is also given in the option that's also correct so gum infiltration occurs in M4 M5 if I change the word gum infiltration with chloroma chloroma is the I eyeball the orbit involvement then the answer will become M2 in the same question the answer will become how many of you got it w classification is the not important here P classification is important R the question comes on the P classification okay AML with worse prognosis tell me poor prognostic Factor bad prognostic Factor 821 translocation this is good one inversion 16 this is also good one normal cytogenetics is good one not the complex one but monosome 7 7 CU it's a bad one so the answer is this one you can see monomi 7 is poor but you can see you can see 821 is good one here you can see 821 inversion 16 is also good one but the 7 Q is bad one so you have to learn this table got my point got my point one more question for you translocation character stick in acute prom myotic leukemia you first tell me acute prom myotic lukemia is what is it m0 M1 M2 Ive told you the classification m0 M1 M2 M3 onwards I told you how to learn M3 M4 M5 m6 and M7 how to learn that I told you trick to learn what is the trick acute prootic leukemia Milotic milom monocytic arthrotic and meiotic so they are asking prootic the prootic is M3 so basically they are asking the translocation in M3 so I asked you I told you to learn the translocation in M2 the translocation is 821 in M3 it's 1517 and in M4 it's inversion 16 currently they are asking in M3 So my answer is 1517 currently they are asking in M3 so it is a two-step question first reading the question you have to see acute prootic glucemia is M3 and what is the mutation in M3 it's 1517 so answer is 1517 if in the same question it is 1517 and M3 how many of you got it if I ask you M2 then answer will become 821 and if I ask you in M4 answer will become in in verion 16 so basically you have to learn it separately iur rods are seen in lymphoblast or myoblast lymphoblast or myoblast not in iblast megablast obviously so obviously the iods are seen and I guess everyone know it's myoblast this is a way to differentiate how we differentiate myoblast from the lymphoblast you can see in the myoblast we have IOD here but in lymphoblast we don't have IOD these all are your previous year questions of different exams you can see DIC occurs in which one we know DIC occurs in M3 but what is the name of M3 what is M3 is it acute promic glucemia or acute milom monotic this one is M3 this one is M4 this is CML and this is autoimmun htic anemia they are out of stock and we don't consider them as differential although so correct answer is M3 so correct answer is a I guess you all are right so this is a way we approach this is a way we approach okay one more image based question is there there is a 16year old leukemia patient who is having decreased platel late look at the age look at the age age is always important platel late is less okay prolonged PT and apt I mean bleeding time is more so thrombocytopenia and peripheral smear is so combine the clues look at the age look at the image and look at the thrombocytopenia so combine all three and tell me the translocation tell me the combined translocation so here you can see maximum all these cells are same they are not different so it is school uniform appearance and in the cytoplasm I can see the granules I mean this Rod like materials this is I Rod although image is not very good but here you can see the I rods appreciate the iur rods so appreciate the iur rods the cell is full of are your Rod so basically these are fot cells and maximum pagot cells they all are pagot cells maximum pagot cells are seen in M3 and the mutation in M3 is again 1517 so it's a indirect question first based on the question clinical history and based on the image come on the diagnosis it is a leukemia with maximum fot cell maximum fot cell occur in M3 and the mutation in M3 is 1517 that's why the answer is 1517 how many of you got it got it the next question maximum iots are seen in course the answer is M3 I told you many times okay so it's the same question yeah non-pacific EAS is positive in all AML except NC non-pacific East race NSE e is positive only in three AML which three M3 M4 and M5 I told you it it's positive in M3 M4 M5 but not in M6 so correct answer is m6 because they're asking except so correct answer is m6 got it so it is positive in M3 M4 M5 you can see but not in M6 okay got it so so we are done with that I guess many questions we have covered we are done with AML CML and AML let's start the next one Al can I start how many of you are ready can we start how many of you are with full energy yet H still in energy can we continue can we continue the next one say yes H definitely I will consider Muhammad definitely I will cover I will cover all these topics you can text it here one by one I will schedule it okay so let's come on the next topic that is Al the third leukemia we have covered this covered this now we will cover this and finally this one and we will have a comparative table of all four so let's come on Al so what is happening in Al now in Al what will happen listen listen until now we have covered two now so let me revise you what happened in CML AML and then come on in CML CCC in CML all these five cells were mutated the name of the mutation is 922 translocation and they all fiber moving in the blood that is CML okay we have already seen that in AML only myoblast was mutated we know the three type of mutation it's 8:21 it was uh 1517 translocation and it was inversion 16 because of which only Milo blast was coming in the blood and that was known as Al okay now we are coming on Al in Al the mutation occur in lymphoblast so only lymphoblast will come in the blood only lymphoblast will come in the blood not others only lymphoblast will come in the blood so that is Al so that is Al how many of you got it so because lymphocytes are of two type B lymy and T lymy so that's why Al is of two type pre B B cell Al or pre cell they occur in children see the age group they typically occur in children so you know the age group here age group I told you more than 50 years here I told you 15 to 40 years and here I'm telling you in children if if it is preb cell it occurs 3 to 5 years and if it is pre cell it occurs in adolescent but both of them are children they are todlers or they are children so basically it's a leukemia of children so basically if you are getting a question there's a child or in this age group and having leukemia only one option is there that is Al so please look the age and compare the age of all of them so it occurs in children here only lymphoblast is coming so in the pathogenesis here I told you here all five are coming myoblast prosite myosite met miloy and band form these five are coming in the blood here only myoblast is coming here only lymphoblast is coming in the blood so this is Garden Party appear this is schol uniform with a rod this is schol uniform without Aur rod that's it it is as simple as that I hope you all are learning it say yes if you got it huh SLE TB I will cover it all don't worry one by one okay CH first understand the leukemias here okay tell me the pathogenesis tell me the mutation in Pre B cell the mutation is hyperploidy most commonly hyperploidy or hypoploidy either the chromosome increase in number more than 46 chromosome or decrease in number less than 46 so hyperploidy or hypoploidy can be there loss of mutations can be there and one of the mutation is 922 you say what 922 but 922 Fusion abl BCR Fusion we have seen in CML you are teaching Us Al I taught you this one is in CML so in CML as well as Al in both of them 922 translocation occur so here also Fusion formed a BCR here also a BCR Fusion formed I I'm telling you in the pathogenesis here also we have 922 translocations of fusion Gene is formed here also 922 transation Fusion Gene is formed so here abl BCR Fusion Gene the size is 21 kilon and here the a BCR Fusion Gene you know how it is formed the same way it is formed the transation The Exchange take place but here the size of the fusion Gene is only 190 kilodalton so that is the you know someone was asking now 210 and 190 kilodalton so we have to see the size based on the size we can identify the fusion Gene size here also abbl BCR Fusion Gene here also abbl BCR Fusion Gene but based on the size we can identify is it CML or is it Al how many of you got it although this is the only mutation which occurs here here it is one of the minor mutation the major mutation is hyperploidy or hypoploid it is one of the minor but in CML it is the only mutation give me a thumbs up people please interact please say give me a feel that I'm teaching you live say yes if you got it say yes and in Pre T Cell the mutation is not Gene the mutation occurs in the not Gene so what are the mutations here either hyperploidy or hypoploid or 922 or not Gene these are the mutations here and based on uh the size of the fusion Gene we can differentiate is it CML or is it Al so we can differentiate according to Pap classification AML was of eight types m0 2 M7 but based on fap classification a is only of three type there is no l0 we directly have L1 L2 L3 we have only three type we don't have L Zer we have only three type L1 L2 L3 you can see L1 L2 L3 L1 is most common having best prognosis L3 is rare and having worst prognosis you can see this is the rare worst prognosis okay so that is L1 L2 L3 now here you can see here you can see the bone marrow failure features here also here only cell is lymphoblast the mutation occur in the lymphoblast which mutation I told you various mutation either hyperploidy or hypoploid or 922 translocation or not gene mutations because of Any mutation this become cancer cell it keep on doing mitosis uncontrolled mitosis mitosis mitosis it will replace everything else so no RBS are formed patient have anemia no platelet are formed patient are beding manifestation although the lymphoblast are many so WBC count will be more but they are the immature cell so patient is highly prone to infection so these are the three features which are common for all Leukemia how many of you got it but here along with the leukemia features patient have you know organ infiltration so organ infiltration occurs in AML also in Al also but the organs will be you know some some unique organs are there here in Al also organ infiltration is there so here the lymphoblast are coming in the blood first in the marrow these lympho blast replace everything else okay then it is spilled in the blood after coming in the blood it will move in various organs which organ enumerate them it can go in the bone it can go in the lymph node it can go in the Spen it can go in the liver it can go in the mediastinal lymph nodes it can go in the manes and it can goes in the testes in the boy in the male I mean so these three things are unique which are present in Al but not in AML and these are common in both these are common in both and gum infiltration and chloroma was unique there you're getting my point so I'm telling you AML I'm telling you a l l okay I taught you here only myoblast will do the uncontrolled mitosis and spill in the blood and after coming in the blood the myoblast will move in various organs here the lymphoblast will do the uncontrolled mitosis from the bone marrow is spilled in the blood and from the blood it will go in various organs so that is the two type of the leukemias we are comparing okay here I told you in both of them liver infiltration is there hpom pomal is in both of them lymph node infiltration lympho adenopathies in both of them kidney infiltration in both of them okay so these are the bone infiltration in both of them it is common but there is something unique organs here some unique organs here so here the unique organs is gum infiltration and chloroma chloroma is the orbit so orbit that is chloroma and gum infiltration is unique here orbit infiltration is seen in M2 and gum infiltration seen in M4 and M5 I told you here the unique is mediastinal lymph nodes mediastinal lymph nodes manages manages and testes testes that is not there but these organs are common which are infiltrated in both of them but in CML there is no infiltration there is no organ infiltration I hope you are getting say yes say no a I hope you have joined late I have already taught you the nap score there okay so you can go back in the session where I have taught you the differential diagnosis of the CML there I taught you the N score in detail in much detail okay so coming on the lab diagnosis of Al currently I'm teaching you Al okay so Al you can see the blood picture the hemoglobin is less the plat late is less obviously in the blood you get only one cell only one cell only one cell which cell it's lymphoblast you can see all cells schol uniform appearance all the cells are same school uniform appearance they all are lymphoblast all the cells are same they are lymphoblast we are done with this one we are done with this one we are done with this one compare people compare open your eyes and compare them see here we get only one cell myoblast here we get only one cell lymphoblast so this is also school uniform appearance this is also school uniform opum but here we are getting the IR rods in the cytoplasm people and here there is no IR rod these are Milo these are LMO blast and here we are getting five type of cells we are getting myoblast prosite myosite metam myosite band form neutral usable Bas monoy it is a garden party appearance a beautiful garden party where everyone is in different beautiful dress how many of you got it people now if the peripheral smar is provided to you will you be able to identify the type of leukemia till now the last one is Ping that I will teach you now then we will do the comparison of all four at one place and one shot say yes so that is lymphoblast here we are getting only lymphoblast see this image can also come one type of cell all the cells are same it's only one type it's not garden party school uniform so it's school uniform is it with Aur Rod or without Aur Rod none of the cell have Aur Rod so they all are lymol okay so you can get any cells so they all are lymphoblast you can see all of them are lymphoblast all all of them are lymphoblast all of them are lymphoblast you can compare now we are done with this coming on the bone marrow again the cellularity is more but this time the leukemic cells are lymphoid not myoid this time the blast is lympho blast rbcs are less wbcs are less obviously in the cytogenetics we have already seen you can get hyperploidy hypoploidy 922 Notch so in the cytogenetics you will get the exact nutrition and cytochemistry also I taught you in the cytochemistry also I taught you you have to compare the five stains to differentiate the myoblast from lympho blast okay now you can get confused sometime you can see ma'am this is also school uniform appearance listen listen and this is also school uniform what if I miss this Aur Rod you are seeing only Aur Rod is the difference if I miss this Aur Rod what I will make wrong diagnosis I will give wrong treatment I cannot do that so use five special stain what are the five special stain these are these myoblast you can see all these cool uniform cells Milo blast they are moo positive they are Sudan black positive and they are positive but they are past negative and acid phosphotase negative these are past positive and acid phosphotase positive so you can see the Cy chemistry is absolutely different so lymphoblast are pass and acid phosphatase positive and myoblast are moo Sudan black and NSP positive so cytochemistry may you have to perform all five together so that Crystal Clear diagnosis so you have to perform all five together you can see here so AML Al currently I want Al so in Al only these two are positive you can see which two pass and asset posties these are positive here and these are negative in these are negative in AML rather in AML these three are positive moo San black and NC which are negative here so based on this we can do the diagnosis say yes got it yes so that is the diagnosis treatment again we don't have any targeted therapy in CML we have targeted but here we don't have targeted so we do bone marot transplant the best treatment if the donor is available H matching is done otherwise chemotherapy is the the option in the chemotherapy but the chemotherapy drugs are different there in AML we have seen the chemotherapy drugs as thuin we have seen cytosin arabinoside here we have visten pralon anthracyclin that is donor Robin and adamin and L asperis so these are the chemotherapy drugs we give here and we give the symptomatic treatment for anemia we give blood transfusion for trombocytopenia we give PL transfusion that is a symptomatic treatment that is not cure okay got it prognostic factors finally the prognostic factors we have good prognosis we have bad prognostic factors 2 to 10 years itur on children I'm teaching you Al I'm teaching you Al itur on children 2 to 10 years age group is gr good but extremes are bad less than two more than 10 both extremes are bad the same was there in AML okay here also extremes are bad in females female child the prognosis is good in male child the prognosis is bad in whites the prognosis is good but in Blacks the prognosis is bad it's genetically okay if the CNS involvement manages involved ment media lymph nodes involvement testicular involvement is there prognosis is um uh if involvement is there if no involvement prognosis is good but if their involvement is there obviously the prognosis is bad okay hyper Ploy is good hypop Ploy is bad please learn that please learn that okay 922 here is bad okay so please learn the important prognostic factors we will solve certain mcqs and move on the last leukemia that is C quickly okay so coming on some mcqs what is the prognostic indicator of huh female female gender is good if the WBC count is less than 50,000 it's good Okay Age more than one 1 to 10 is good okay less than one more than 10 is bad but hypoploid is bad hyperploid is good hyperploid is bad you can see hyperploid is good hyperploid is bad so you can see hyperploid is bad remaining three are good so you have to learn the prognostic factors of all of them okay got it so past periodic acid shift past stain past stain shows block positivity in which is it show block positivity in myoblast or lymphoblast or monoblast or mocar blast so pass is used to differentiate um myoblast and lymphoblast in myoblast it's negative in lymphoblast it's positive lymphoblast so you see pass is one of the stain that is differentiating the two and acid phosph these are the two stains which are positive in lymphoblast but not in myoblast instead of pass if the question is done acid phosphatase so pass and acid phosphates both them are positive in lymphoblast but the moo Sudan black and NSC are positive in myoblast not lymphoblast okay so that is the thing one more question on the prognostic factor we can skip Now read the next question see the age 12 year old male age is important gender is important see 12y old so we are talking about a child okay a male child having fatigue fatigue means anemia so imagine a 12year old child having anemia on physical examination there is palpable axillary and Inu lymphoadenopathy so the lymph nodes are enlarged various lymph nodes are enlarged the Spen is also pable so patient have spomal patient have lymphoadenopathy and peripheral smear images given to you in the peripheral smear I can see all the cells are looking same cool uniform op of SN garden party now try to search the urod in any of them do you find the urod no we are finding hardly any cytoplasm hardly any cytoplasm most of them they don't have any cytoplasm they are lymphoblast so is the option Al or CL or infectious mononucleosis or iron deficiency anemia of course it's leukemia so which leukemia is it Al or CL huh looking at the age and looking at the image my diagnosis is Al and you all are right CLL never occur in this age group CL occurs after 80 years reading the age only rule out this option reading the age don't look at the image reading the age only rule out this option rule out Ru out it never occur in children in children we have only one leukemia and the image is also supporting that say yes if you all got it the correct answer is a So based on that you get many question image based question so till now we have covered three till now we have covered three leukemia so age group is different in all three okay so let me come on the last one are you ready shall I start the last one CLL and I will do a comparative analysis of all four so let's come on the last one that is CLL so let's come on the last chronic lymphocytic leukemia also known as small lymphocytic lymphoma sometime this converts into into lymphoma so it is CL or SL one and the same ages over 60 years median age 60 years it occurs in old age only so usually 60 years or more than 60 years okay so here what is happening listen listen people come back listen everyone listen start from the beginning so start from CML what was happening in CML in CML CM the five cells were mutated these five they all were mutated they were doing uncontrolled mosis and they all five were coming in the blood that is the CML we have seen that okay now the second I taught you is EML in EML only Milo blast was mutated doing uncontrolled mitosis and it was coming in the blood so in AML only myoblast was coming in blood Okay the third I taught you is Al in which lymphoblast was doing uncontrolled mitosis it was mutated and only lymphoblast was coming in the blood that is Al now last I want to teach you clll so you tell me in clll what will come in the blood you tell me in CFL what CL what will come in the blood can you guess then I will tell you so what will exactly come in the blood can you tell me what will come in the blood huh say yes say no say something respond people write down in the chat box fast quick what will come in the blood here none of the blast will come in the blood in CLL mature lymphocytes come in the blood mature lymphocytes come in the blood CLL you see we all have lymy I'm also having lymy but I don't have CL so what do you mean by mature lymy here the mature lymphocytes are there but they are not normal they are mutated lymy in them mutations are there I will tell you the exact mutations are there no no lymphoblast don't come here bisma it is the only leukemia where no blast is coming neither mitol blast nor lymphoblast none of the blast is coming in the blood here the mature lymphocytes which are mutated they are coming in the blood and in the blood you will get only one type of cell that is mature lymphocyte again school uniform appearance but only one a lymphocyst if you're getting only lympho blast it's Al you are getting mature lymphocytic the mature lymphocyte it is not normal it is not normal normally we have 20 to 50% of lymy in blood here 99% are lymphocytoid no neutrophil no yopy no basophil nothing else so here the complete marrow is filled with lymphocytes of 13 deletion of 11 deletion of 17 11 133 and 17 the odd numbers and and the triom of 12 H so deletion of 11 13 and 17 I mean monosomy monomi of 11 13 and 17 but the triom of 12 okay so these are the deletion of 13 is most common that will lead to uh you know that will lead to uh uncontrolled mitosis and lymphocytes and the lymphocytes are spilled in the blood so here 99% cells are the lymphocytes you got it so here also the same three clinical features anemia bleeding disorders infection because they most of the cells are lymy they will replace everything else so no RBC patient have anemia no platelet patient have beding disorder and most of the cells are only mature but abnormal lymphocytes so patient have high susceptivity for infection but lymphoadenopathy heal spomal can also present okay lab diagnosis of course hemoglobin and plate will be less and WBC will be normal to more you can see here this is the parital spere now compare you ma'am okay what is this listen listen listen this is the patient please understand this is a patient the age of the patient is 80 years okay the age AG of this patient is 80 years and patient is complaining of anemia patient is having lethargy patient is having bleeding disorders patient is having frequent infection and lymphoadenopathy so looking at the age and the symptom I'm suspecting the patient is having leukemia so what I will do say m take a parital smear and I'm suspecting the patient is having CLL and my diagnosis is right my suspicion is right if my suspicion is right the blood sample contain only one cell with cell is it lymphoblast no no no it is lymphocyte which are mutating so this this these all cells are mature lymphocytes which are mutated now please listen they are mutated they are abnormal they are not normal lymy their cell wall is very fragile so what happens after taking it in a test tube what you will do say ma'am I will make a smear I will take a slide how to make a smear tell me the process say ma'am it's very easy take a drop here take a drop here and take a take a spreader at 45° put the spreader and spread it and make a tongue shaped smar I guess you know that so you take a spreader and with a a spreader you make a smear so why I'm telling you that so because here when you spread and make a tongue shape smear now most of the lymphocytes sometime they get ruptured because they are abnormal lymphocyte lymphocytoid and spread them some of them are complete but some of them will rupture some of them will rupture they will burst the bursted it smudge or basket cells are the ruptured lymphocyst so you can say it's a slide artifact it's a slide artifact these are not present in patient muscels are not present in patient's blood they're not present in test tube but why making the slide because of the spreader the lymphocytosis cells how many of you got it so in this slide what you will get you will see ma'am these all are mature lymphocyte but some of them are ruptured and I can see this is a smudge cell this is a smudge cell how many of you got it you can see the same here you can see only one type of cell mature lymphocyte you can see and some of them are ruptured which are known as smudge cell smudge cell or basket cell how many of you got it people say people respond so smudge cell or basket cell are the degenerated forms they are produced because of the fragile lymphocytes the lymphocytes are very fragile they get ruptured you get McQ on that yes due to wenting problem absolutely right Clary absolutely right so in the cell wall uh in the cell wall I told you there is a problem in the won and that's why they are very fragile and by making a slide they get raptured so that is a smart cell how many of you got it so we are done here with the peripheral smear also so we can compare all four finally finally we can compare all four the four leukemia peripheral Mir in front of you let's compare come back let's compare you can see these two are myoid these two are lymphoid you can see the acute chronic acute chronic in AML let's start with AML in AML compared to Al compared the two acute versions in the two acute versions both of them are school uniform appearance here only one cell myoblast here only one cell lymphoblast you would say m' how to differentiate myoblast from lymphoblast myoblast have moderate cytoplasm with aod aod that is fot cells here scanty cytoplasm or no cytoplasm and no aod so myoblast lymphoblast that's it now coming on The Chronic versions coming on The Chronic versions see The Chronic version of CML here see The Chronic version of CLL here see The Chronic versions so in CML it's a garden party appearance you get many type of cells especially the five precursors myoblast prosite myosite metam myoy band form along with neutr osophy basophil and monocytes you get everything Garden Party and here again school uniform but no blast here we have blast here we have blast here we have blast here we have no blast in CL we have mature lymoc it's not a blast but it's abnormal it's mutated and the ruptured form is the SMUD cell so we can get sm so you see the paral smear and compare all five give me a thumbs up people no one will simplify the super simplified version of leukemias here the comparative you can looking at the parip meere you can make it out which type I'm now tell me the age of all four tell me the pathogenesis of all four likewise everyone got it h everyone yes definitely have a schedu a session on the lymphoma if many students are demanding the same okay now coming on the lab diagnosis of Cl let me finish CL let me so in the blood picture hemoglobin is less plate is less WBC is more and the cells are most of the cells I told you they are lymphocytes imop phenotyping you can do so it is uh uh it is a leukemia of the B lymphocytes so here all the markers of the B lympocytes are present like CD cd19 cd20 surface IGM igd along with cd23 and cd5 these are B cell markers because here the mature b cells are present now which are mutated and lymph node biopsy you can do in the lymph node biopsy you can see the pseudo follicles can be present normal follicles are eased and instead of that pseudo follicles are there and you can see if you if you zoom out if you are zooming it and doing the magnification inside the pseudo follicles you can see the small round FOID sell with scandy cytoplasm that's it okay we are done treatment no Treatment available palea symptomatic treatment no chemotherapy no treatment no targeted therapy nothing is available prognosis is usually very poor the poor prognostic factors are 11 Q delion 17 Q Delon or tri2 no hyper somatic hypermutation or presence of Notch mutation these are the poor prognostic factors we are done read the question tell me the answer 80y old man look at the age age is always important people age is always important presented with a painless cervical lymphoadenopathy and the peripheral smear is given to you look at the age look at the symptom look at the image combine the three and tell me the diagnosis what you see in the image in the image I can see only one type of cell these are lymphocytes you can see these are not blast blast are big in size they are small small they are not blast they hardly have any cytoplasm and along with that the biggest glue given to you the ruptured versions are given to you that these are the SM cell so correct answer is C and you all are right okay got it can we go ahead can we go ahead SMUD cells are found in of course the question is very easy I guess everyone can answer smut cells are found in CL of course so smut cells are the ruptured ruptured mature lymphocytes that is the smudge cells also known as basate cell the basic mutation is in the uh bantin there is abnormality in the v that's why it get ruptured while we are making the smear so it's a slide artifact in CLL basic basically which Ty which type of cell is predominating is it b lymy or t lymy or is it simple lymy or is it monoy so basically it's a simple lymoc side which is proliferating here and coming it is mutated proliferating and spilled over in the blood so we are done we are done with the four types of leukemia can we compare it once for a while and end the session you can text me further more sessions you require on which topic and let me tell you what I have planned further for you so let me compare the PO leukemias first you know the definition tell me the group of all four so CML occurs after 50 years AML occur 15 to 40 years Al occur in children and cl occurs 60 60 to 80 years so you can see the age group is entirely different okay please note down looking at the age exceptions are there but looking at the age itself you can have a guess which type of leukemia they are talking in the pathogenesis tell me the mutation here here uh the mutation is taking place in five cells tell me first cells myoblast pryo it miloy mosite and band form I will tell you the mutation also here mutation taking place only in myoblast here mutation taking place in lymphoblast here mutation taking place in mature lymphocytes not in Blast now tell me the mutation tell me the mutation people here only one mutation is there 922 translocation only one mutation is there here various types are there specifically eight types are there so mutation is important in M2 M3 and M4 although mutation occurs in all but important in our syllabus is these three so in m m 2 it's 821 translocation in M3 it's 1517 translocation and in M4 it's inversion 16 translocation okay here in Al in lymphoblast we have two types we have two types what are the two types we have B uh preb cell and pre cell in the preb Cell It's hyperploid hypoploidy and 922 translocation in the T Cell It's Notch mutation you will say ma'am we have 2 to 922 yes we have 922 here also here also so we have Fusion formed there also there also but here the size of the fusion Gene is 210 kilodalton and here the size of the fusion Gene is 190 kilodalton based on which we can differentiate coming finally on the mutations in clll so we have 11 13 and 17 monomi they are dels or monomi dels or monomi and 12 trii the most important among them is 13 so this is the pathogen you have to learn say yes people say yes so I have taught you the age of all and I have taught you the pathogen of so here you have to understand one thing this mutation whatever I have mentioned this mutation this mutation this mutation this this is occurring in with cell so here all these five cells come in the blood so Garden Party appearance here only one cell come here only one cell comes and here also one cell will come so these are the school uniform appearance but here along with the lymy they will rupture so you will get smudger cells also so comparing the peripheral smear of all four makes a sense you can see the we can compare the paral smar so you can see here we are getting only one one cell that is myoblast here with IOD here getting one cell lympo blast no IOD here getting five cell myoblast milite prosite metam myoy and band form and here getting only one cell lymphocytes cell I guess it's Crystal Crystal super duper clear to all of you so paral smear is super duper clear to all of you now the most important thing one more thing wait wait wait clinical feature compare the clinical feature of all food we will compare every aspect every aspect I will make leukemia you know I will crush it and definitely I will make it a fun for you after 5 minutes leukemia will be nothing for you you know you can answer any question based on the leukemia in your whatever exam you are targeting doesn't matter or anyways so here clinical features so anemia thrombocytopenia that is bleeding disorders and infection that occurs here also here also here also here also because here the uh five cells are replacing everything here myoblast are replacing everything your lymphoblast are replacing everything and here lymph are replacing everything that's why patient have anemia in all three patient have trombocytopenia in all four patient have infection in all four so this is the common in all four but here we don't have organ infiltration but here we have organ infiltration so lymphoadenopathy occurs in both of them hepat spomal bone pain occurs in both of them okay it is uring organ nutrition here specific organs in AML is gum and chloroma here specific organs is mediastinal lymph node testes and manes that is specific manages occurs here also but less specific so that you have to learn sometime here cervical lymphoadenopathy or other lymphoadenopathy present here also but only lymphoadenopathy so this is the organ infiltration we have seen but we never have organ infiltration in CML please learn that in CML no organ infiltration coming on the lab diagnosis and treatment part okay coming on the lab diagnosis of all of them let me tell you the lab diagnosis let me erase it and tell you the lab diagnosis okay in the lab diagnosis you tell me the cytochemistry I mean special stain of all of them on which you frequently get the question so here the special stain is nap or lap scod which is reduced here to differentiate it from licite reaction here it's moo positive Sudan black positive and NS positive okay these three things are negative here but this one is pass positive and acid phosphatase positive which are negative here and and here we don't have any special we have uh immunochemistry here we don't have cytochemistry so it's cd19 cd20 IGM positive H surface marker cd23 positive so you have to learn the immunochemistry treatment portion I have told you so only one of them have targeted therapy CML and the name of the targeted therapy is imip here we have imip we don't require bone marot transplant here bone marot transplant with chemotherapy bone marot transplant with chemotherapy here palea therapy prognostic factors you have to learn good bad good bad good bad good bad got it huh give your feedback you got the leukemias was it easy the same you can compare here also if you didn't like this diagram you can see the same here appreciate appreciate appreciate myoblast here appreciate the I rods appreciate lymphoblast here no I rods appreciate all pipe myoblast prom myoy miloy matoy band form and appreciate only one cell that is lymy along with the smudger cell here appreciate if you have any doubt ask if you have any doubt please ask got it got it now if you are preparing for your com exam that is neat PG in India fmg in in India or you are preparing for some abroad exams like USM or plab so I have simultaneously we have solved the mcqs but if you are preparing for second Prof University exam and you have a theory paper on leukemia so this is a list of University exam questions I will provide you in the notes you can read the long questions I provided to you from leukemia you should be prepared for that and short questions are also provided to you so all the long questions short questions I'm damn sure you can answer it now so whatever exam you are targeting you are prepared people you can note down this 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which is important for you so you can connect with me on various social media platforms on WhatsApp on in Instagram on telegram if you wish so just scan it or you can take a snapshot you can scan it later that's all about it thank you for your time for your attention for your patience thank you so much what about the next sessions we have scheduled so currently in the February we are having these eight sessions this one is already done and today we have covered this complete lukemia in one shot today 7th of February I guess after 12 it's already 8th anyways um on 12th of February again the same timing 1 p.m. 1: p.m. complete contracep devices on one shot now you have contraception in multiple subjects sometime you read it in OBG OBC and Gynecology you read it in community medicine you written multiple subjects I will compile all of them at one place in one shot and you get many questions from the contraceptive devices so it will compile and compare and we will do a more simplified version of that after that we have a session on hyper sensitivity we have session on triage we have session of tmia this month only we have we have I'm going to compile complete micology in one shot on huge demand of students all fungus at one place in one shot and we have a session on all pharmacokinetics important things in entire pharmacology pharmacokinetics at one place in P so these all are important sessions this month you can take the snapshot the timing of all session is same it's 10:00 p.m. onwards in the Night 10 to 12 10 to 1 whatever 1:00 a.m. approx so 2 to 3 hour session because in the late night students are more you know awaken I have seen huh the late most of the students nowadays they are late night hours I have seen instead off early morning I know wake up so that's why we have scheduled the sessions late night thank you so much good night I hope you have enjoyed the session you have learned a lot of it so don't forget to share your feedback it's important for us to improve thank you so much and to be if you want to be odd one you if you want to be number one you have to be odd one so never uh be afraid if you are different from others never be afraid okay so thank you so much bye-bye good night all the best so I am ending the session and uh just a second give me a minute I would like to wish best of luck to the students who are going to appear in the exam in the next few months many students second Pro MB students texted me to take this topic because they are going to appear in the exam this month next month in the next few days so on huge demand I have scheduled this so I want to wish best luck to all those students thank you so much wishing all the best to all of you bye-bye good night