Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries, characterized by the clonal proliferation and progressive accumulation of functionally incompetent, mature-appearing CD5-positive B lymphocytes in the peripheral blood, bone marrow, lymph nodes, and spleen. CLL accounts for approximately 25-30% of all adult leukemias with an incidence of approximately 4-5 per 100,000 annually. The median age at diagnosis is 70 years, with a male-to-female ratio of approximately 2:1. The pathogenesis of CLL involves the clonal expansion of B lymphocytes that have arrested at an intermediate stage of B-cell differentiation. These CLL cells characteristically co-express the B-cell markers CD19, CD20 (dim), and CD23 with the T-cell marker CD5 -- this aberrant CD5 expression on B cells is the immunophenotypic hallmark of CLL and distinguishes it from other B-cell lymphoproliferative disorders. The CLL cells also express dim surface immunoglobulin (sIg), typically IgM and/or IgD, reflecting their origin from antigen-experienced B cells. The fundamental defect in CLL is not excessive proliferation (the CLL cells actually divide slowly) but rather defective apoptosis -- the CLL cells accumulate because they fail to...