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
Rl. Alexander et al., 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, LEUK RES, 25(10), 2001, pp. 875-881
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.