ROLE OF SURAMIN AS AN IL-1 INHIBITOR IN SUPPRESSION OF ACUTE MYELOGENOUS LEUKEMIA PROGENITOR PROLIFERATION

Interleukin-1 (IL-1) modulates both autocrine and paracrine growth-sti mulatory mechanisms of acute myelogenous leukemia (AML) cell prolifera tion. Recent studies show that blocking the interaction between IL-1 a nd its receptor may suppress this proliferation. Because suramin, a po lysulfonated naphthylurea originally described as an antitrypanosomal agent, was found to inhibit the binding of several growth factors to t heir receptor, we tested its effect on AML progenitor proliferation. W e first examined the effect of suramin on murine EL-4.6.1 cells that e xpress type I IL-1 receptors and found that suramin inhibited the bind ing of IL-1 to its receptor. We then tested the effect of suramin on A ML progenitors using bone marrow samples from 17 patients with AML. In all experiments, suramin inhibited AML blast proliferation in a dose- dependent fashion at concentrations ranging from 30 to 240 mu M. IL-1 beta (100 U/mL) partially reversed this inhibitory effect. Suramin als o inhibited normal early and mature hematopoietic progenitors, as asse ssed by both the delta assay and the mixed colony culture assay; howev er, at the same concentration, suramin suppressed the colony growth of colony-forming units granulocyte-macrophage (CFU-GM) by only 45% comp ared with an 89% suppression of AML progenitors. IL-1 beta did not neg ate this inhibitory effect, which suggests that another growth inhibit ory mechanism might be operative. Our data suggest that suramin may in hibit AML progenitor proliferation by blocking the interaction of IL-1 and its receptor; therefore, further studies are warranted to evaluat e suramin's therapeutic potential in patients with AML.