Human cytokines suppress apoptosis of leukaemic CD5+ B cells and preserve expression of bcl-2.

Leukaemic CD5+ B cells obtained from B cell chronic lymphocytic leukaemia (B-CLL) patients rapidly undergo apoptosis during in vitro culture. This is associated with down-regulation in expression of bcl-2. Spontaneous apoptosis of these cells contrasts their enhanced longevity in vivo and suggests that apoptosis-inhibitory factors may be responsible for the accumulation of leukaemic cells in B-CLL. The effect of different cytokines on apoptosis and bcl-2 expression was examined in six populations of leukaemic CD5+ B cells. Consistent with previous data, IL-4 and IFN-gamma suppressed apoptosis in 6/6 and 5/6 cell populations, respectively. Interestingly, the ability to suppress apoptosis in leukaemic CD5+ B cells was also found to be a property of IL-2, IL-6, IL-13 and TNF-alpha. In the presence of these cytokines, 10-40% more viable cells were detected, compared with unstimulated cultures. Enhancement of cell viability and suppression of apoptosis were associated 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 may be targets for treating this malignancy.