BCL-X IS THE MAJOR PLEIOTROPIC ANTI-APOPTOTIC GENE ACTIVATED BY RETROVIRAL INSERTION MUTAGENESIS IN AN IL-3 DEPENDENT BONE-MARROW-DERIVED CELL-LINE

In order to identify genes capable of inhibiting apoptosis induced by different pathways, without inducing proliferation we have performed r etroviral insertion mutagenesis in the IL-3 dependent bone marrow deri ved Baf-3 cell line, Out of 200 mutants obtained in three separate mut agenesis experiments, four mutants were resistant to multiple apoptosi s inducing pathways (including growth factor starvation, staurosporine , etoposide and cyclosporin A) and did not proliferate in the absence of IL-3, These four mutants overexpress the bcl-X gene following a ret roviral insertion 5' of the translation initiation site, These results indicate that the bcl-X gene is a major pleiotropic anti-apoptotic ge ne in Baf-3 cells, They also suggest that the Bcl-2 family of genes mi ght be the only one capable of inhibiting apoptosis induced by multipl e pathways without inducing cell proliferation.