BCL-2 INHIBITS T-CELL-MEDIATED CYTOLYSIS OF A LEUKEMIA-CELL LINE

The beta gene becomes dysregulated in its expression in a wide variety of human cancers and has been shown to block both spontaneous and dru g-induced cell death, thus conferring a selective survival advantage o n malignant cells. The biochemical mechanism by which bcl-2 promotes c ell survival remains enigmatic but appears to involve a downstream eve nt in an evolutionarily conserved cell death pathway. Here we report t hat gene transfer-mediated increases in Bcl-2 protein levels in the hu man leukemia line Jurkat render these cells more resistant to inductio n of DNA fragmentation and cytolysis by a cloned T-cell. The killing m echanism used by these particular T-cells was consistent with apoptosi s, as opposed to necrosis, in that DNA degradation occurred as a prely sis event. The findings raise the possibility that dysregulation of bc l-2 gene expression could play a role in the avoidance of immune surve illance mechanisms by cancer cells.