Apoptosis deregulation in CLL.

The description of apoptosis and the identification of the genes that regulate it have proved pivotal to our understanding of how cancer cells accumulate and ultimately cause morbidity and mortality. It has become increasingly clear that in CLL the balance between the pro- and anti-apoptotic members of the BCL2 family of apoptotic regulatory proteins is critical in the development and clinical progression of CLL. Furthermore, the apoptotic potential of the CLL cell determines chemotherapy sensitivity and ultimately progression-free and overall survival. The unravelling of the BCL2 story in CLL has led to the development of a whole new class of therapeutic agents-the BH3 mimetics-which are significantly more targeted than conventional chemo-immunotherapy and therefore promise potent clinical activity coupled with reduced toxicity.