Biochemical and genetic control of apoptosis: Relevance to normal hematopoiesis and hematological malignancies

GENETIC CHANGES involving oncogenes and tumor suppressor genes contribute t o the deregulated expansion of malignant cells. While some of these changes result in increased proliferation, others contribute to an increase in cel l numbers by inhibiting apoptosis (programmed cell death).(1) Because cytot oxic drugs or irradiation result in cell killing by apoptosis, the genetic changes underlying malignancy often reduce the ability of these agents to d estroy malignant cells.(1,2) The elucidation of the pathways involved in th e regulation of apoptosis in normal and malignant hematopoietic cells is th erefore likely to contribute to the development of improved therepeutic sta tegies in the treatment of leukemia and lymphoma. This review first summari zes recent advances in the understanding of the control of apoptosis. Examp les of how this control is altered in leukemic cells is then described.