Chronic lymphocytic leukemia: A disease of dysregulated programmed cell death

Chronic lymphocytic leukemia (CLL) represents a quintessential example of a human malignancy which is caused principally by defects that prevent cell turnover due to programmed cell death rather than by alterations in cell cycle regulation. In the vast majority of patients, CLL cells are predominantly G₀ quiescent lymphocytes that gradually accumulate in the patient's body not because they are dividing more rapidly than normal, but because they are surviving too long. Investigations of the genetics of CLL therefore seem likely to teach us much about the molecular mechanisms that regulate programmed cell death (PCD). Moreover, since defects in the pathway for PCD can render neoplastic cells resistant to the cytotoxic effects of chemotherapeutic drugs and radiation, investigations of the aberrant regulation of cell death in CLL may also prove informative for gaining a better understanding of drug- and radiation-resistance mechanisms. In this review, I summarize current knowledge about the cytogenetic abnormalities associated with CLL and the role of deregulated cell death in the pathogenesis of this most common of the adult leukemias.