Prevention of programmed cell death in burkitt lymphoma cell lines by bcl‐2‐dependent and ‐independent mechanisms

Burkitt lymphoma (BL) cell lines which retain the phenotypic characteristics of the freshly‐isolated tumour cells (group I cells) readily enter programmed cell death (apoptosis) in response to a variety of triggers. By contrast, isogenic BL cells which are phenotypically altered as a result of activation of their resident EBV genome (group‐III cells) are highly protected from apoptosis. Phenotypic changes in group‐III cells include the up‐regulation of the oncogene, bcl‐2. Expression of the 26‐kDa bcl‐2 protein in group‐1 BL cells following gene transfer was found to afford protection from apoptosis: the degree of protection was proportional to the amount of bcl‐2 protein expressed. When group‐1 bcl‐2 transfectants were compared with their group‐III counterparts it was found that, whilst bcl‐2 made a significant contribution in protecting from entry into apoptosis, hyper‐expression of bcl‐2 protein in group‐1 cells (well beyond that of group‐III cells) was necessary to attain the high levels of protection observed in group‐III cells. These results suggested that additional, bcl‐2‐independent, survival mechanisms could operate in BL cells. In support of this notion it was also found that: (I) prolonged culture of group‐1 lines in vitro resulted in enhanced survival in the absence of bcl‐2 up‐regulation, and (2) exposure of group‐1 cells to interferon‐α triggered a bcl‐2‐independent protective response. The molecular mechanisms of both the bcl‐2‐dependent and ‐independent survival pathways remain to be determined. © 1992 Wiley‐Liss, Inc.