HUMAN CYTOKINES SUPPRESS APOPTOSIS OF LEUKEMIC CD5(-CELLS AND PRESERVE EXPRESSION OF BCL-2() B)

Leukaemic CD5(+) B cells obtained from B cell chronic lymphocytic leuk aemia (B-CLL) patients rapidly undergo apoptosis during in vitro cultu re. This is associated with down-regulation in expression of bcl-2. Sp ontaneous apoptosis of these cells contrasts their enhanced longevity in vivo and suggests that apoptosis-inhibitory factors may be responsi ble for the accumulation of leukaemic cells in B-CLL. The effect of di fferent cytokines on apoptosis and bcl-2 expression was examined in si x populations of leukaemic CD5(+) B cells. Consistent with previous da ta, IL-4 and IFN-gamma suppressed apoptosis in 6/6 and 5/6 cell popula tions, respectively. Interestingly, the ability to suppress apoptosis in leukaemic CD5(+) B cells was also found to be a property of IL-2, I L-6, IL-13 and TNF-alpha. In the presence of these cytokines, 10-40% m ore viable cells were detected, compared with unstimulated cultures. E nhancement of cell viability and suppression of apoptosis were associa ted with a delay in down-regulation of bcl-2. These results suggest a role for autocrine and paracrine growth factors in the pathogenesis of B-CLL, and indicate that cytokines which prevent apoptosis in vitro m ay be targets for treating this malignancy.