Apoptosis in chronic lymphocytic leukemia

CHRONIC lymphocytic leukemia (CLL) is characterized by a low growth fraction and expansion of a subset of long-lived lymphocytes. However, during short-term culture, CLL cells spontaneously die via apoptosis. The propensity of CLL cells to undergo apoptosis in vitro correlates with clinical features suggesting that an apoptosis-resistant phenotype occurs with disease progression. Despite data demonstrating that nucleoside analogs require DNA synthesis for cytotoxicity in proliferative cells, CLL cells rapidly undergo apoptosis after exposure to fludarabine and 2-chlorodeoxyadenosine. Demonstration of apoptosis in patients requires sensitive techniques due to rapid clearance by the reticuloendothelial system. Although evidence of bcl- 2 rearrangements is lacking in CLL, bcl-2 expression is often elevated and has been correlated with in vitro apoptosis and drug resistance. A precise understanding of the mechanisms involved in apoptotic cell death should have direct implications for cancer therapy.