Suppression of chronic myelogenous leukemia colony growth by interleukin-4

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

    Research output: Contribution to journalArticle

    15 Citations (Scopus)

    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

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    Leukemia, Myelogenous, Chronic, BCR-ABL Positive
    Interleukin-4
    Granulocyte-Macrophage Progenitor Cells
    Growth
    Granulocyte Colony-Stimulating Factor
    Interleukin-1
    Interleukin-3
    Bone Marrow
    Granulocyte-Macrophage Colony-Stimulating Factor
    Interleukin-6
    Blood Cells
    Megakaryocytes
    Phytohemagglutinins
    Conditioned Culture Medium
    Erythropoietin
    Granulocytes
    Monocytes
    Cultured Cells
    Down-Regulation
    Erythrocytes

    ASJC Scopus subject areas

    • Cancer Research
    • Hematology

    Cite this

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

    Suppression of chronic myelogenous leukemia colony growth by interleukin-4. / Estrov, Zeev; Markowitz, Avi; Kurzrock, Razelle; Wetzler, Meir; Kantarjian, Hagop M.; Ferrajoli, Alessandra; Gutterman, Jordan U.; Talpaz, Moshe.

    In: Leukemia, Vol. 7, No. 2, 02.1993, p. 214-220.

    Research output: Contribution to journalArticle

    Estrov, Z, Markowitz, A, Kurzrock, R, Wetzler, M, Kantarjian, HM, Ferrajoli, A, Gutterman, JU & Talpaz, M 1993, 'Suppression of chronic myelogenous leukemia colony growth by interleukin-4', Leukemia, vol. 7, no. 2, pp. 214-220.
    Estrov Z, Markowitz A, Kurzrock R, Wetzler M, Kantarjian HM, Ferrajoli A et al. Suppression of chronic myelogenous leukemia colony growth by interleukin-4. Leukemia. 1993 Feb;7(2):214-220.
    Estrov, Zeev ; Markowitz, Avi ; Kurzrock, Razelle ; Wetzler, Meir ; Kantarjian, Hagop M. ; Ferrajoli, Alessandra ; Gutterman, Jordan U. ; Talpaz, Moshe. / Suppression of chronic myelogenous leukemia colony growth by interleukin-4. In: Leukemia. 1993 ; Vol. 7, No. 2. pp. 214-220.
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    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.",
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