Growth factors can protect B-chronic lymphocytic leukaemia cells against programmed cell death without stimulating proliferation.
The proliferation and survival of B-chronic lymphocytic leukaemia (B-CLL) cells may be regulated by autocrine growth factor loops. Furthermore, it has been suggested the reduction in lymphocytosis following therapy with interferon-alpha may be associated with the interruption of autocrine growth factor production. We have therefore examined the effects of a number of cytokines on the proliferation of B-CLL cells, and also on the regulation of programmed cell death, and the role of interferon-alpha in these systems. In the ten patients studied, neither interferon-alpha alone or together with either interferon-gamma, IL1, IL4, IL6, TNF, or serum containing high levels of soluble CD23 was able to induce proliferation of B-CLL cells. Incubation with TPA or IL2 resulted in variable proliferative responses. Co-incubation with interferon-alpha enhanced TPA-induced proliferation in 4 cases, but reduced IL2-induced proliferation in all cases studied. In contrast, all the cytokines studied were able to protect B-CLL cells against programmed cell death, both spontaneous and that induced by hydrocortisone, with the exception of TNF. These data suggest a role for interferon-alpha in disrupting autocrine survival pathways rather than inhibiting proliferation.
Jewell
A P
AP
Department of Haematology, University College London Medical School, UK.
Lydyard
P M
PM
Worman
C P
CP
Giles
F J
FJ
Goldstone
A H
AH
D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000473:pathology*; D011994:Recombinant Proteins; D013268:Stimulation, Chemical; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D016207:Cytokines; D004273:DNA, Neoplasm; D007370:Interferon Type I; D011994:Recombinant Proteins; D014316:Tritium; D013936:Thymidine