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In vitro effect of r-verapamil on acute myelogenous leukemia blast cells: studies of cytokine secretion and cytokine-dependent blast proliferation

  • Original Article
  • Acute Myelogenous Leukemia, R-Verapamil
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Abstract

The in vitro effect of the dextroisomer r-verapamil on blast cells derived from patients with acute myelogenous leukemia (AML) was studied. R-verapamil caused a dose-dependent inhibition of AML blast proliferation in the presence of stem-cell factor, leukemia inhibitory factor, interleukin 4, interleukin 6, and interleukin 10 when these cytokines were tested both alone and in different combinations. R-verapamil also inhibited the growth of clonogenic AML blast cells. The antiproliferative effect was not specific for AML blast cells, because r-verapamil also inhibited cytokine-dependent proliferation of blast cells derived from patients with acute lymphoblastic leukemia. The inhibitory effects of r-verapamil and anti-IL1 serum were additive, suggesting that the antiproliferative effect of r-verapamil does not depend solely on inhibition of IL1-mediated effects. Although r-verapamil inhibited spontaneous AML blast proliferation, for a majority of patients it caused only minimal, if any, inhibition of spontaneous cytokine secretion (IL1α, IL1β, TNFα, IL6) by AML blast cells. Thus, although inhibition of IL1 effects may contribute in certain patients to the antiproliferative effect of r-verapamil, mechanisms other than IL1 inhibition seem to be more important in mediating the effects of r-verapamil.

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Abbreviations

ALL :

Acute lymphocytic leukemia

AML :

acute myelogenous leukemia

cpm :

counts per minute

ELISA :

enzyme-linked immunosorbent assay

G-CSF :

granulocyte colony-stimulating factor

GM-CSF :

granulocyte-macrophage colony-stimulating factor

IL :

interleukin

IF :

leukemia inhibitory factor

PBMC :

peripheral blood mononuclear cells

RR :

relative response

SCF :

stem cell factor

TNFα:

tumor necrosis factor α

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Authors and Affiliations

  1. Medical Department B, Haukeland University Hospital, University of Bergen, N-5021, Bergen, Norway

    Øystein Bruserud & Ingrid Nesthus

  2. Sektion für Transplantationsimmunologie und Immunhaematologie, Medizinische Klinik II, Tübingen, Germany

    Graham Pawelec

Authors
  1. Øystein Bruserud
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  2. Ingrid Nesthus
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  3. Graham Pawelec
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Bruserud, Ø., Nesthus, I. & Pawelec, G. In vitro effect of r-verapamil on acute myelogenous leukemia blast cells: studies of cytokine secretion and cytokine-dependent blast proliferation. Cancer Chemother. Pharmacol. 37, 70–78 (1995). https://doi.org/10.1007/BF00685631

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  • DOI: https://doi.org/10.1007/BF00685631

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