Lecture on Leukemias

Introduction

Leukemia: Blood cancer characterized by abnormal proliferation of white blood cells (WBCs)
Types of WBCs: Granulocytes (neutrophil, eosinophil, basophil), Agranulocytes (lymphocytes, monocytes)

Originates in bone marrow from hematopoietic stem cells
Myeloid progenitor: RBCs, platelets, myeloblast (progenitor for neutrophil, eosinophil, basophil, monocyte)
Lymphoid progenitor: Lymphoblast (progenitor for lymphocyte, T-cells, B-cells)
Precursors for Neutrophil: Myeloblast > promyelocyte > myelocyte > metamyelocyte > band form > neutrophil
Precursors for Lymphocyte: Lymphoblast > prolymphocyte > lymphocyte

Mutation: Oncogenes or tumor suppressor genes result in uncontrolled mitosis
Acute vs. Chronic: Based on the type and maturity of cells proliferating
Blast cells in bone marrow < 5% normal; > 20% in acute leukemias
Chronic leukemias: Involvement of later precursor cells

Based on Cell Origin and Progression
- Acute vs Chronic
- Myeloid vs Lymphoid
Four Major Types: CML, AML, ALL, CLL

Introduction: Leukocytosis with predominantly immature forms, splenomegaly, Philadelphia chromosome (95% cases)
Age Group: Middle-aged to elder (>50 years)
Pathogenesis: Mutation affecting myeloid progenitors (922 translocation, BCR-ABL fusion gene, abnormal tyrosine kinase -> uncontrolled mitosis)
Diagnosis: Garden Party appearance; WBCs with immature forms; positive for Philadelphia chromosome
Phases: Chronic, Accelerated, Blast
Treatment: Targeted therapy with Imatinib
Differential Diagnosis: Differentiate from leukemoid reaction via NAP score

Introduction: Proliferation of myeloblasts, more common in younger adults (15-40 years)
Pathogenesis: Multiple specific mutations (e.g., 1517, 821, and inversion 16); only myeloblasts in blood
FAB Classification: Eight subtypes (M0 to M7)
Diagnosis: Myeloblasts with Auer rods (POSITIVE M.P.O, SBB, NSC), absence of PAS and acid phosphatase
Clinical Features: Bone marrow failure, organ infiltration
Treatment: Bone marrow transplant, chemotherapy (specific drugs: cytarabine, doxorubicin)
Prognosis: Better with certain mutations, younger age, fewer leukocytes

Introduction: Proliferation of lymphoblasts, primarily in children (3-5 years, adolescents)
Pathogenesis: Pre-B (hyper/hypoploidy, 922), pre T (Notch mutations); only lymphoblasts in blood
FAB Classification: Three subtypes (L1 to L3)
Diagnosis: Lymphoblasts without Auer rods (POSITIVE PAS and acid phosphatase, NEGATIVE M.P.O, SBB, NSC)
Clinical Features: Bone marrow failure, organ infiltration (mediastinal lymph nodes, testes)
Treatment: Bone marrow transplant, chemotherapy (specific drugs like prednisolone, vincristine)
Prognosis: Better with certain age groups, white race, female gender

Introduction: Proliferation of mature lymphocytes, most common in older adults (>60 years)
Pathogenesis: Mutations affecting mature lymphocytes (deletion 11, 13, 17; trisomy 12)
Diagnosis: Peripheral smear shows mature lymphocytes, smudge cells (slide artifacts)
Clinical Features: Anemia, lymphadenopathy
Treatment: Palliative care, supportive treatments
Prognosis: Generally poor, managed by symptomatic treatment

General trend: Mature to immature cell involvement from chronic to acute leukemias
Diagnostic features: Cytochemistry, morphological appearance (GPA vs School Uniform appearance)
Treatment outlines: Imatinib (CML), bone marrow transplant, chemotherapy
Prognosis tied closely to specific genetic mutations and patient demographics

Leukemias represent a spectrum of hematological malignancies, with significant overlap in clinical presentation but distinct pathophysiological mechanisms
Understanding the cell line origin, specific mutations, and clinical manifestations is crucial for accurate diagnosis and appropriate treatment

Age of presentation, genetic mutations, diagnostic criteria (special stains, cytogenetics)
Clinical features and prognosis indicators
Differentiation strategies between types, such as NAP score, presence of Auer rods, and smudge cells