急性髓性白血病患者原始细胞上高亲和力白细胞介素-3受体的表达与白喉毒素/白细胞介素-3融合蛋白的细胞毒性相关。

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.

作者信息

Alexander R L, Ramage J, Kucera G L, Caligiuri M A, Frankel A E

机构信息

Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.

出版信息

Leuk Res. 2001 Oct;25(10):875-81. doi: 10.1016/s0145-2126(01)00034-0.

DOI:10.1016/s0145-2126(01)00034-0

PMID:11532521

Abstract

Diphtheria fusion proteins are a novel class of agents for the treatment of chemotherapy resistant AML. We prepared DT(388)IL3 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(388)IL3 cytotoxicity (>1 log cell kill) was seen in nine of 25 samples (36%). There was a significant correlation between DT(388)IL3 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(388)IL3.

摘要

白喉融合蛋白是一类新型的用于治疗化疗耐药性急性髓系白血病（AML）的药物。我们制备了由人白细胞介素-3（IL3）与白喉毒素（DT(388)）的催化和转位结构域融合而成的DT(388)IL3，并评估了其对患者AML原始细胞的活性。使用放射性标记的IL3激动剂（SC-65461）测量循环原始细胞中IL3受体的数量和亲和力。92%患者的原始细胞同时具有高亲和力和低亲和力的IL3受体。在25个样本中的9个（36%）观察到DT(388)IL3的细胞毒性（细胞杀伤>1个对数）。DT(388)IL3的细胞杀伤对数与原始细胞高亲和力IL3受体密度之间存在显著相关性（P=0.0044）。这些结果表明，特异性高亲和力IL3结合是患者白血病原始细胞对DT(388)IL3敏感性的一个重要因素。