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Effect of interleukin‐1, tumor necrosis factor‐α, and interferon‐α on the blast cells of acute myeloblastic leukemia
Author(s) -
Carter Anna,
SilvianDraxler Iiana,
Tatarsky Iiana
Publication year - 1992
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.2830400402
Subject(s) - autocrine signalling , tumor necrosis factor alpha , acute myeloblastic leukemia , dna synthesis , granulocyte macrophage colony stimulating factor , biology , cytokine , alpha interferon , leukemia inhibitory factor , myeloid leukemia , cancer research , leukemia , microbiology and biotechnology , immunology , interferon , cell culture , interleukin 6 , in vitro , biochemistry , genetics
In this study, we further established the role of interleukin‐1α (IL‐1α), interleukin‐1β, tumor necrosis factor‐α (TNF‐α), and interferon‐α (IFN‐α) as regulators of proliferation of acute myeloid leukemia (AML) cells. AML cells from 8 of 15 patients incorporated high levels of 3 H‐thymidine ( 3 H‐TdR) in the absence of exogenous growth factors. The spontaneous DNA synthesis could be abrogated with monospecific antibodies directed toward IL‐1α, IL‐1β, or TNF‐α, as well as with antigranulocyte‐macrophage colony‐stimulating factor (GM‐CSF). Human recombinant GM‐CSF reversed the inhibitory action of each of these antibodies and reinduced DNA synthesis in AML cells. Thus, in these cases, constitutively produced IL‐1 or TNF‐α had stimulated the synthesis of GM‐CSF, which resulted in GM‐CSF‐dependent proliferation of AML blasts. Exogenous IL‐1 up‐regulated the endogenous production of GM‐CSF, suggesting a positive regulation of autocrine growth factor production. We also present evidence that TNF‐α may exert both stimulative as well as inhibitory effects on DNA synthesis in AML cells. The enhancing effect of TNF‐α was mediated through the induction of GM‐CSF production, as stimulation of DNA synthesis in AML blasts could be abrogated with anti‐GM‐CSF antibody. A concentration‐dependent inhibitory effect of TNF‐α on 3 H‐TdR incorporation into AML blasts was observed only when these cells were grown in the absence of GM‐CSF. Finally, we show that human recombinant IFN‐α is a potent inhibitor of AML cell proliferation in vitro. © 1992 Wiley‐Liss, Inc.