Definition:
Acute leukemias are malignant neoplasms of hematopoietic progenitor cells characterized by:
- Rapid proliferation of immature white blood cells (blasts)
- Replacement of bone marrow with blasts
- Sudden onset and fast progression
They are classified as either:
- Acute Lymphoblastic Leukemia (ALL) – from lymphoid progenitors
- Acute Myeloid Leukemia (AML) – from myeloid progenitors
Classification:
- Acute Lymphoblastic Leukemia (ALL): More common in children
- Acute Myeloid Leukemia (AML): Primarily affects adults; may arise de novo or from myelodysplastic syndromes
Etiology:
General Causes:
- Radiation (e.g., therapeutic or environmental): Causes DNA damage to hematopoietic stem cells
- Chemicals: Benzene exposure
- Drugs: Cytotoxic chemotherapy (alkylating agents, topoisomerase inhibitors)
- Viruses: Human T-cell lymphotropic virus type 1 (HTLV-1) → Adult T-cell leukemia
- Genetics:
- Down syndrome (especially predisposes to AML)
- Fanconi anemia
- Bloom syndrome
- t(12;21), t(9;22) in ALL
AML-specific:
- May develop secondary to:
- Myelodysplastic syndrome (MDS)
- Chemotherapy or radiation therapy
ALL-specific:
- Most common in children (peak incidence: 2–5 years)
Pathogenesis:
- Genetic mutations disrupt normal differentiation of hematopoietic stem cells
- Blasts proliferate uncontrollably and infiltrate bone marrow, crowding out normal hematopoiesis
- Leads to pancytopenia:
- Anemia → ↓ RBCs
- Leukopenia or non-functional leukocytosis → ineffective immune defense
- Thrombocytopenia → bleeding tendencies
- Blast cells may infiltrate:
- Liver, spleen, lymph nodes (especially in ALL)
- CNS, testes, skin (notably in ALL and AML variants)