Suppression of chronic myelogenous leukemia colony growth by interleukin-4

Zeev Estrov, Avi B. Markowitz, Razelle Kurzrock, Meir Wetzler, Hagop M. Kantarjian, Alessandra Ferrajoli, Jordan U. Gutterman, Moshe Talpaz

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    15 Scopus citations

    Abstract

    Interleukin-4 (IL-4) is a cytokine with pleiotropic activities. In normal bone marrow cultures grown in the presence of either granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3), IL-4 suppresses granulocyte-macrophage colony-forming unit (CFU-GM) proliferation but it enhances the colony-stimulatory effect of granulocyte colony-stimulating factor (G-CSF). We studied the effect of IL-4 on chronic myelogenous leukemia (CML) bone marrow or peripheral blood cells from 30 patients using the CFU-granulocyte-erythrocyte-monocyte-megakaryocyte colony culture assay. In several repetitive experiments, IL-4 inhibited CFU-GM colony replication by 24 to 65% in a dose-dependent fashion at concentrations ranging from 0.01 to 10 μg/ml when patients' cells were cultured in the presence of erythropoietin alone or with phytohemagglutinin-conditioned medium, GM-CSF, or IL-3. The addition of 100 U/ml of IL-1β to the CML cultures partially reversed the inhibitory effect of IL-4. Incubation of CML low-density peripheral blood cells with IL-4 resulted in down-regulation of IL-1β and IL-6 production in three of four samples, suggesting that the suppressive effect of IL-4 is mediated by inhibition of IL-1 and by other mechanisms including inhibition of IL-6 production. In contrast to the stimulatory effect exerted by IL-4 on G-CSF-dependent CFU-GM progenitor proliferation in normal marrow, the addition of IL-4 to CML cultures grown in the presence of G-CSF resulted in a divergent effect: suppression of CML CFU-GM in two, stimulation in three, and no significant effect in two CML patients' samples. It is therefore possible that IL-4 may have an in vivo antiproliferative effect in a subpopulation of CML patients.

    Original languageEnglish (US)
    Pages (from-to)214-220
    Number of pages7
    JournalLeukemia
    Volume7
    Issue number2
    StatePublished - Feb 1993

    ASJC Scopus subject areas

    • Hematology
    • Oncology
    • Cancer Research

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  • Cite this

    Estrov, Z., Markowitz, A. B., Kurzrock, R., Wetzler, M., Kantarjian, H. M., Ferrajoli, A., Gutterman, J. U., & Talpaz, M. (1993). Suppression of chronic myelogenous leukemia colony growth by interleukin-4. Leukemia, 7(2), 214-220.