MODULATION OF COLONY STIMULATING FACTOR (CSF) DEPENDENT GROWTH OF ACUTE MYELOID-LEUKEMIA BY TUMOR-NECROSIS-FACTOR

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  • 1 January 1990
    • journal article
    • research article
    • Vol. 4  (1) , 37-43
Abstract
In this study we demonstrate that tumor necrosis factors (TNF.alpha. and TNF.beta.) are potent modulators of the in vitro proliferation of human AML cells. Blast cells from 11 cases of acute myeloblastic leukemia (AML) were incubated with recombinant TNF.alpha. or TNF.beta. in serum-free 3H-TdR uptake and colony culture systems in the presence or absence of recombinant interleukin-3 (IL-3), granulocyte macrophage colony-stimulating factor (GM-CSF), G-CSF, or M-CSF. Depending on the supplemented CSF, TNF could upregulate or suppress AML blast proliferation. Enhancement of AML growth by TNF was observed in the presence of IL-3 (in 9 of 11 cases in 3H-TdR assayl 6 of 9 cases in colony assay) and GM-CSF in 8 out of 11 cases in 3HTdR assay; 4 of 9 cases in colony assay. In certain cases in which il-3 or GM-CSF alone was unable to induce proliferative responses of AML cells, the simultaneous addition of TNF elicited colony growth and DNA synthesis suggesting a synergistic action between TNF and IL-3 or GM-CSF. In contrast, TNF suppressed G-CSF induced growth (9 of 10 cases in 3H-TdR assay; 5 of 6 cases in colony asay). TNF could also stimulate DNA synthesis (in 2 out of 11 cases) or colony formation (in 2 out of 9 cases) in AML cultures without the addition of other growth factors. Experiments with neutralizing antibodies and specific radioimmunoassays for individual CSFs showed that the synergistic and antagonistic effects of TNF on AML cells. The opposing consequences of exposure of AML blasts to TNF are of interest in view of our understanding of the pathophysiology of AML growth and the in vivo application of recombinant cytokines in AML patients.