Biochemical and Genetic Control of Apoptosis: Relevance to Normal Hematopoiesis and Hematological Malignancies

GENETIC CHANGES involving oncogenes and tumor suppressor genes contribute to the deregulated expansion of malignant cells. While some of these changes result in increased proliferation, others contribute to an increase in cell numbers by inhibiting apoptosis (programmed cell death).(1) Because cytotoxic drugs or irradiation result in cell killing by apoptosis, the genetic changes underlying malignancy often reduce the ability of these agents to destroy malignant cells.(1,2) The elucidation of the pathways involved in the regulation of apoptosis in normal and malignant hematopoietic cells is therefore likely to contribute to the development of improved therepeutic stategies in the treatment of leukemia and lymphoma. This review first summarizes recent advances in the understanding of the control of apoptosis. Examples of how this control is altered in leukemic cells is then described.