Etiology

• No identifiable cause or risk factors in most cases

• Prior bone marrow damage due to alkylating chemotherapy or ionizing radiation

• Adult T-cell leukemia/lymphoma is linked to infection with HTLV.

• Genetic or chromosomal factors

  • Down syndrome: Risk of ALL is, like that of AML, 10–20 times higher in patients with Down syndrome compared to the general population.

  • Neurofibromatosis type 1

  • Ataxia telangiectasia

• No identifiable cause or risk factors in most cases

• Pre-existing hematopoietic disorder (most common identifiable cause)

  • Myelodysplastic syndromes

  • Aplastic anemia

  • Myeloproliferative disorders (e.g., osteomyelofibrosis, CML)

• Environmental factors

  • Alkylating chemotherapy

  • Ionizing radiation

  • Benzene exposure

  • Tobacco

• Genetic or chromosomal factors

  • Down syndrome: The risk of AML is, like that of ALL, 10–20 times higher in patients with Down syndrome compared to the general population.

  • Fanconi anemia

B-cell ALL (∼ 80–85% of cases (e.g., Mature B-cell ALL (also known as Burkitt leukemia)

T-cell ALL (∼ 15–20% of cases)

• French-American-British (FAB) classification

• The WHO classification

• Acquired somatic mutations (chromosomal translocations and other genetic abnormalities) in early hematopoietic precursors → clonal proliferation of a lymphoid or myeloid stem cell line and arrest in cell differentiation and maturation in early stages of hematopoiesis → rapid proliferation of abnormal and dysfunctional blasts (with impaired apoptosis pathways) → accumulation of leukemic white blood cells in the bone marrow → disrupted normal hematopoiesis → leukopenia (↑ risk of infections), thrombocytopenia (↑ bleeding), and anemia

• Immature blasts enter the bloodstream → infiltration of other organs (particularly the CNS, testes, liver, and skin)