Chronic Myeloid Leukemia

Definition

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of hematopoietic stem cells characterized by uncontrolled proliferation of myeloid cells and the presence of the BCR-ABL1 fusion gene (Philadelphia chromosome).

Epidemiology

• Accounts for 15–20% of adult leukemias
• Median age at diagnosis: 55–60 years
• Slight male predominance
• Incidence: ~1–2 cases per 100,000 population per year
• Rare in children and young adults

Etiology

• Acquired genetic abnormality: t(9;22)(q34;q11), producing BCR-ABL1 fusion gene
• Resulting in constitutively active tyrosine kinase driving proliferation
• No clear hereditary pattern
• Ionizing radiation exposure is a potential risk factor
• Other environmental exposures: less well established

Pathophysiology

• BCR-ABL1 tyrosine kinase activates multiple signaling pathways promoting cell proliferation and inhibiting apoptosis
• Clonal expansion of myeloid cells leads to leukocytosis
• Bone marrow hypercellularity with granulocytic predominance
• Progression through chronic phase → accelerated phase → blast crisis if untreated
• Splenomegaly develops due to extramedullary hematopoiesis