Bcl-2 family proteins and the regulation of programmed cell death in leukemia and lymphoma

Members of the bcl-2 gene family play a central role in regulating the relative sensitivity and resistance of cells to a wide variety of apoptotic stimuli. The first member of this multigene family ,bcl-2, was discovered by virtue of its involvement in the t(14;18) chromosomal translocations commonly found in non-Hodgkin’s lymphomas [1–4]. Deregulation of the bcl-2 gene either by translocations in B-cell lymphomas or through other mechanisms in several other types of cancer, including acute and chronic leukemias, contributes to neoplastic cell expansion by prolonging cell survival rather than by accelerating rates of cell division [5–8]. The Bcl-2 protein also can protect tumor cells from apoptosis induced by radiation and nearly all cytotoxic anticancer drugs [9–12], thus potentially contributing to treatment failures in patients with cancer [13–16]. Several additional homologues of bcl-2 have recently been discovered in humans and other mammals, revealing the presence of a multigene family [17–20]. Moreover, homologues of bcl-2 have been discovered in some DNA viruses, including Epstein-Barr virus (EBV), which plays a significant role in the pathogenesis of some types of non-Hodgkin’s lymphomas and Hodgkin’s disease [21]. Interestingly, some members of the bcl-2 gene family function as inhibitors of cell death, similar to bcl-2, whereas others are promoters of apoptosis that oppose the actions of the Bcl-2 protein.