IGHTY-FIVE PERCENT of follicular lymphomas and E 20% of diffuse B-cell lymphomas have a characteristic t (14; 18) translocation.’.’In this translocation, the proto-oncogene BCL2 at chromosome segment 18q21 is juxtaposed with the Ig heavy chain locus at 14q32, resulting in deregulated expression of BCL2. 3-6 The discovery that BCL2, unlike oncogenes studied previously, functions in preventing programmed cell death (PCD) instead of promoting proliferation established a new class of oncogene^.^.^ The initial observation of BCL2’s ability to enhance cell survival was that overexpression of BCL2 increased the viability of certain cytokinedependent cells upon cytokine withdrawal. In interleukin-3 (IL-3)-dependent pro-B-cell lines and promyeloid cell lines, BCL2 overexpression prolonged cell survival upon IL-3 withdrawal and maintained the cells in Go7,’The observation was extended to IL-4-and granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent cells’ and in certain IL-2-dependent” and IL-6-dependent” cells. BCL2 was also capable of protecting T cells against a variety of apoptotic signals, including glucocorticoids, y-irradiation, phorbol esters, ionomycin, and cross-linking of cell surface molecules by anti-CD3 antibody. The protective effects were observed in T-cell hybridomas transfected with BCL2 and in thymocytes and peripheral T cells from transgenic mice with expression of BCL2 under the control of the proximal promoter of lck (ZC~ J’?’~ or the Ig heavy chain enhancer