IN-VITRO EFFECT OF R-VERAPAMIL ON ACUTE MYELOGENOUS LEUKEMIA BLAST CELLS - STUDIES OF CYTOKINE SECRETION AND CYTOKINE DEPENDENT BLAST PROLIFERATION

The in vitro effect of the dextroisomer r-verapamil on blast cells der ived from patients with acute myelogenous leukemia (AML) was studied. R-verapamil caused a dose-dependent inhibition of AML blast proliferat ion in the presence of stem-cell factor, leukemia inhibitory factor, i nterleukin 4, interleukin 6, and interleukin 10 when these cytokines w ere tested both alone and in different combinations. R-verapamil also inhibited the growth of clonogenic AML blast cells. The antiproliferat ive effect was not specific for AML blast cells, because r-verapamil a lso inhibited cytokine-dependent proliferation of blast cells derived from patients with acute lymphoblastic leukemia. The inhibitory effect s of r-verapamil and anti-IL1 serum were additive, suggesting that the antiproliferative effect of r-verapamil does not depend solely on inh ibition of IL1-mediated effects. Although r-verapamil inhibited sponta neous AML blast proliferation, for a majority of patients it caused on ly minimal, if any, inhibition of spontaneous cytokine secretion (IL1x , IL1 beta, TNFx, IL6) by AML blast cells. Thus, although inhibition o f IL1 effects may contribute in certain patients to the antiproliferat ive effect of r-verapamil, mechanisms other than IL1 inhibition seem t o be more important in mediating the effects of r-verapamil.