so let's say that you've got this Hamato poetic stem cell and this guy's basically starting his choose-your-own-adventure game it can choose to differentiate into a myeloid stem cell or a lymphoid stem cell sometimes we just call these precursor cells blasts if it goes the myeloid path it can go on to be all sorts of specialized cells like red blood cells monocytes granulocytes or megakaryocytes alternatively it could choose the lymphoid stem cell route and it can go on to become B cells or T cells of the immune system these adventures of the hematopoietic stem cells are usually happening all the time and new cells are like always being created in acute leukemia though they lose this ability to differentiate or mature into one of these cells so for example they might get to the myeloid blast part of the adventure but can't differentiate any further and when they can't go anywhere they start to build up so you end up with this buildup of these blasts or stem cells and since this is all happening in your bone marrow this buildup will also happen in your bone marrow so if you took a sample of somebody's bone marrow that didn't have acute leukemia you probably notice that the percentage of their blast cells is about one to two percent which would be normal if there are greater than 20% blast cells in the bone marrow though we define that as acute leukemia when all these blast cells start to build up they get crowded and they crowd out or sort of get in the way of normal cells differentiating so what happens is you end up presenting with a loss of cells that you'd normally produce in the bone marrow like if you had a loss of red blood cells you develop anemia where you might have symptoms of fatigue or maybe you're missing platelets so you get thrombocytopenia and have problems with bleeding or neutrophils and neutropenia and start getting more infections usually symptoms like this can come about relatively quickly which is why we say that it's acute leukemia eventually these blasts build up to a point where they start to spill out into the bloodstream which typically causes your white blood cell count to go up so if you took a peek at a blood smear there's a couple things to look for first look at how large these guys are compared to the normal cells another thing is that they'll be pretty immature judging by this relatively low amount of cytoplasm alright great so we figured out that it's a blast cell but what kind of blast cell is it lymphoid or myeloid hmm tough to say this is important though because if they have a buildup of milo blasts they'll actually have acute myeloid leukemia whereas if they have a buildup of lymph oblast they'll have acute lymphoblastic leukemia and these two are very different and need very different treatments so what we're gonna do is we're gonna look for certain markers for the lymphoblast the most important markers that they'll have this positive nuclear staining for T DT in the cell's nucleus T DT is a DNA polymerase that's present only in the nucleus of the lymphoblasts not in the lymphocytes or the mature cells and not in the milo blasts so if a nuclear stain comes out positive for T DT we know that it's got to be a lymph Oblast right for the myeloblast presence of Milo peroxidase an enzyme indicates that we've got to have a myeloid blast on our hands usually this is done by cytoplasmic staining but you can also look for this like crystallized version of the enzyme called an hour rod under the microscope okay so let's say that we've got a positive test for DNA polymerase T DT meaning that we've got a lymph oblast so we must have a cute lymphoblastic leukemia it actually gets a little more complicated though remember the lineage where a lymphoblasts go on to be either B or T cells well in between they become either B lymphoblasts or T lymphoblasts so really you can have subtype B acute lymphoblastic leukemia or be a ll or T acute lymphoblastic leukemia or T ALL just like we figured out that as a lymph oblast with T DT positivity we can also determine which subtype of lymphoblasts it is based on surface markers the most commonly seen are these B lymphoblasts so BA ll and super important and specific surface markers to look for are c 10 c 19 and c 20 treatment of ba ll usually involves chemotherapy and there's usually a very good response but one thing you have to remember is that the chemotherapy goes into the blood and it can't cross either the blood-brain barrier or the blood testicular barrier so patients will often need prophylactic injection of the chemotherapy to the scrotum and the cerebrospinal fluid if we look at these patients a little more closely at their cytogenetic abnormalities so like abnormalities in their chromosomes we can get an idea of their prognosis if they have a translocation of chromosome 12 and 21 or t12 21 they'll usually have a pretty good prognosis and this tends to happen more in children a 922 translocation or sometimes called ph+ or the Philadelphia chromosome on the other hand is a pretty poor prognosis and this one's seen more in adults okay for the tea lymphoblastic sort they'll usually express surface markers that range from cd2 to cd8 unlike ba ll these blasts do not express C d-10 okay so luckily we've got some helpful mnemonics with T ALL it usually presents as this dynamic mass in the mediastinum so T for thymus and this happens most often in teenagers t for teens so we're gonna call this acute lymphoblastic lymphoma wait why not leukemia well remember that for leukemias the malignant cells float around in the blood where lymphoma means that the malignant cells are forming this mass so in this case it's called lymphoma since it's forming this thymic mass okay so that's all for the a ll type let's switch gears to the AML type which is this accumulation of milo blasts remember that we're looking for an enzyme called milo peroxidase right which can present is these our rods like in this picture this structure right here is an hour rod which is basically like this crystallized aggregate of milo peroxidase which is only found in milo blasts AML unlike a ll is more common in adults between the ages of 50 and 60 and can actually be sub classified in three ways either again by cytogenetic abnormalities the lineage of the milo blasts or by surface markers one important subtype of AML to be aware of is acute promyelocytic leukemia and this is characterized by translocation of chromosomes 15 and 17 so right now we're sub classifying based on cytogenetic abnormalities right chromosomes 15 and 17 this translocation ends up disrupting the retinoic acid receptor which hurts the cell's ability to mature and you get this buildup of promyelocytes these cells also tend to have a lot of our rods which increases the chance of coagulation which makes it a medical emergency due to the risk of disseminated intravascular coagulation or di see one way to treat promyelocytic leukemia is with all-trans-retinoic acid or a tra which is this derivative of vitamin A and this guy binds to the disrupt retinoic acid receptor and actually causes these blasts to mature into neutrophils which eventually go on to die but it does sort of lift some of the leukemic burden since there aren't as many of these blasts floating around so that one was characterized by its cytogenetic abnormalities right but we can also characterized by the lineages so sort of just like lymphoid blasts can go on to be either T or B lymphoblasts you could have an AML like erythroblastosis or mono blast AML all which would involve is proliferation of that type of cell so one that's important to know about is this last one mono blast AML or acute monocytic leukemia so these mono blasts build up and they actually often lack milo peroxidase but what we can look for instead is this infiltration of the patient's gums so check out this image notice how this patients gums are clearly swollen and this is a classic sign of acute monocytic leukemia another important subtype though is mega karaoke clukey mia so a buildup of mega carry ablaze just like the mono blasts these don't have milo peroxidase either but there's this association with Down syndrome before the age of five so this is actually an important point in general patients with Down syndrome have an increased risk of acute leukemia usually acute mega karaoke clukey Mia when it's before the age of five and a ll after the age of five now there are also conditions that aren't necessarily AML but can actually lead to AML and one is called milo dysplastic syndrome which is characterized by this abnormal buildup of blasts in the bone marrow which sounds familiar right but at this point it's below 20% so we don't call it AML yet myelodysplasia meaning bad formation of bone marrow cells often leads patients to have a low blood cell count since the cells aren't developing right which is also called cytokine iya because they have these cytokine ia's they often actually die due to infection or bleeding but they can also progress to acute leukemia if their blast percentage goes over 20% so then they'd have something like AML with a background of Mylo dysplasia and that's an overview of acute leukemia as well some of the more common subtypes of acute leukemia you