High affinity interleukin-3 receptor expression on blasts from patients with acute myelogenous leukemia correlates with cytotoxicity of a diphtheria toxin/IL-3 fusion protein

Diphtheria fusion proteins are a novel class of agents for the treatment of chemotherapy resistant AML. We prepared DT(388)IL3 composed of human inter leukin-3 (IL3) fused to the catalytic and translocation domain of diphtheri a toxin (DT388) and assessed its activity on patient AML blasts. The number and affinity of IL3 receptors in circulating blasts was measured using a r adiolabeled IL3 agonist (SC-65461). Ninety-two percent of patients' blasts had both high and low affinity IL3 receptors. DT(388)IL3 cytotoxicity ( > 1 log cell kill) was seen in nine of 25 samples (36%). There was a significa nt correlation between DT(388)IL3 log cell kill and blast high affinity IL3 receptor density (P = 0.0044). These results show that specific high affin ity IL3 binding is one factor important in the sensitivity of patients' leu kemic blasts to DT(388)IL3. (C) 2001 Elsevier Science Ltd. All rights reser ved.