Role of interleukin-1 inhibitory molecules in therapy of acute and chronic myelogenous leukemia

The poor outcome of conventional therapy of acute and chronic myelogenous leukemias (AML and CML) has prompted several groups to investigate new therapeutic directions. Data from various laboratories, including our own, indicate that both normal and leukemia precursors proliferate in response to growth factors. Furthermore, it has been shown that AML blasts, low-density cells from CML patients with advanced disease, and cultured bone marrow-adherent layers from CML blast crisis patients produce interleukin 1 (IL-1); this molecule may play a pivotal role in driving leukemia cell proliferation through autocrine or paracrine pathways. We have therefore hypothesized that interruption of the IL-1-mediated growth-stimulatory mechanism may suppress leukemia precursor multiplication. In searching for IL-1-inhibitory molecules that may be used clinically, we have investigated the in vitro effects of various IL-1 inhibitors including IL-1 receptor antagonist, soluble IL-1 receptors, and interleukin 4. Our studies suggest that IL-1 inhibitors can suppress clonogenic growth of cultured AML and CML progenitors and may hence be exploitable in clinical trials.