Potent efficacy of chlorpromazine in acute myeloid leukemia harboring KIT-D816V mutation

被引：1

作者：

Rai, Shinya ^{[1
]}

Tanaka, Hirokazu ^{[1
]}

Espinoza, J. Luis ^{[1
]}

Kumode, Takahiro ^{[1
]}

Matsumura, Itaru ^{[1
]}

机构：

[1] Kindai Univ, Fac Med, Dept Hematol & Rheumatol, Osaka, Sayama, Japan

来源：

LEUKEMIA RESEARCH REPORTS | 2021年 / 15卷

关键词：

Acute myeloid leukemia; Kit-d816v; Chlorpromazine; Intracellular trafficking; Receptor tyrosine kinase;

D O I：

10.1016/j.lrr.2021.100256

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Acute myeloid leukemia (AML) is a heterogeneous disease often associated with poor prognosis. We previously showed that the localization of KIT-D816V at endolysosomes is critical to activate aberrant Akt signaling and Chlorpromazine (CPZ) perturbs the intracellular localization, leading to cell death in AML cells with KIT-D816V. We report that daily administration of CPZ, prescribed for controlling anxiety disorder in patient with AML harboring KIT-D816V, led to a dramatic reduction in AML cells. In vitro and in vivo experiments showed that CPZ inhibited the growth and survival of the patient-derived AML cells, implying potent efficacy of CPZ in AML with KIT-D816V.

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