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The bcl-2 gene and protein in malignant lymphomas.

The 14;18 chromosomal translocation, characteristic of a significant fraction of non-Hodgkin's lymphomas, results from an apparent error in immunoglobulin gene rearrangement. Breakpoints for the 14;18 translocation cluster at defined sites on chromosomes 14 and 18 and this clustering has important implications for molecular diagnostic studies of lymphomas. The major effect of the 14;18 translocation is a transcriptional deregulation of the bcl-2 gene resulting in levels of the protein and mRNA that appear to be inappropriate for B cells at a comparable stage of differentiation. Gene transfer studies have demonstrated that inappropriate bcl-2 expression has subtle effects on cellular growth and survival without overt tumorigenic conversion. Biochemical studies have shown that bcl-2 is an integral membrane protein localized to the cytoplasmic side of cellular membranes, suggestive of a role in signal transduction, but no demonstrable biochemical activity has been reproducibly associated with the protein.