title: Bcl-2 family proteins: regulators of apoptosis and chemoresistance in hematologic malignancies.
abstract: Nearly all anticancer drugs presently available to clinicians kill tumor cells by activating an endogenous biochemical pathway for cell suicide, known as programmed cell death or apoptosis. However, many malignant cells develop defects in the regulation of genes that control apoptosis, rendering them resistant to the induction of apoptosis by a wide variety of stimuli, including chemotherapeutic drugs and radiotherapy. The BCL-2 family of proto-oncogenes are critical regulators of apoptosis whose expression frequently becomes altered in human cancers, including some of the most common types of lymphomas and leukemias. The first member of this gene family to be identified was BCL-2, by virtue of its involvement in t(14;18) chromosomal translocations commonly found in B-cell non-Hodgkin's lymphoma (NHL). Subsequently, however, overexpression of Bcl-2 has been reported in a wide variety of cancers, without associated chromosomal translocations. A variety of experiments have provided conclusive evidence that elevations in Bcl-2 expression cause resistance to chemotherapeutic drugs, while decreases in Bcl-2 expression promote apoptotic responses to anticancer drugs. Information about the biochemical mechanisms of action of the Bcl-2 protein and other members of the Bcl-2 family is beginning to suggest strategies for overcoming the cytoprotective effects of Bcl-2 overexpression in lymphomas, leukemias, and other types of cancer.
authors.affiliation: Burnham Institute, Cancer Research Center, La Jolla, CA 92037, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Reed
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000473:pathology; D009154:Mutation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2