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.
Tangye
S G
SG
Department of Cell and Molecular Biology, University of Technology, Sydney, New South Wales, Australia.
Raison
R L
RL
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D018956:CD5 Antigens; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*
D018956:CD5 Antigens; D016207:Cytokines; D007378:Interleukins; D019253:Proto-Oncogene Proteins c-bcl-2; D007371:Interferon-gamma