Protease activation and glucocorticoid-induced apoptosis in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is at present an incurable disease. All of the drugs used in the treatment of CLL induce apoptosis in the cells, and in vitro responses to glucocorticoid or analogs correlate with in vivo sensitivity to these agents. Since CLL lymphocytes accumulate rather than proliferate, the idea that CLL is a disease involving defective apoptosis is particularly attractive. Recent studies have identified many of the central components of the apoptotic pathway that appear to be conserved from one cell type to another. Thus, investigation into the functionality of these molecules should reveal where the defect(s) in apoptosis may lie in CLL cells. Protease activation is a central event during apoptosis. and leads to many of the familiar characteristics of apoptosis. Here we will examine the role of apoptotic proteases in CLL and speculate on their contribution to disease emergence and drug resistance.