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 388IL3 composed of human interleukin-3 (IL3) fused to the catalytic and translocation domain of diphtheria toxin (DT 388) and assessed its activity on patient AML blasts. The number and affinity of IL3 receptors in circulating blasts was measured using a radiolabeled IL3 agonist (SC-65461). Ninety-two percent of patients’ blasts had both high and low affinity IL3 receptors. DT 388IL3 cytotoxicity (>1 log cell kill) was seen in nine of 25 samples (36%). There was a significant correlation between DT 388IL3 log cell kill and blast high affinity IL3 receptor density ( P=0.0044). These results show that specific high affinity IL3 binding is one factor important in the sensitivity of patients’ leukemic blasts to DT 388IL3.