Leukemia: Classification, Molecular Pathology, and NP

Leukemia arises from malignant clonal expansion of hematopoietic precursor cells in the bone marrow, disrupting normal hematopoiesis and leading to cytopenias. Classification is based on cell lineage (lymphoid vs myeloid) and acuity (acute vs chronic). Acute lymphoblastic leukemia (ALL) involves malignant proliferation of lymphoid precursor B-cells (85%) or T-cells (15%), most common in children aged 2-5 years. The Philadelphia chromosome t(9;22) BCR-ABL1 fusion is found in 25% of adult ALL and confers poor prognosis but is targetable by tyrosine kinase inhibitors (imatinib, dasatinib). Acute myeloid leukemia (AML) results from clonal expansion of myeloid progenitors with maturation arrest; the t(15;17) PML-RARA translocation defines acute promyelocytic leukemia (APL), uniquely responsive to all-trans retinoic acid (ATRA) and arsenic trioxide. Chronic lymphocytic leukemia (CLL) involves accumulation of mature but functionally incompetent CD5+ B-lymphocytes resistant to apoptosis due to BCL-2 overexpression; most common adult leukemia in Western countries. Chronic myeloid leukemia (CML) is defined by the Philadelphia chromosome t(9;22) producing BCR-ABL1 constitutive tyrosine kinase activity driving unregulated myeloid proliferation through three phases: chronic, accelerated, and blast crisis. The WHO 2022 classification integrates morphology, immunophenotyping, cytogenetics,...