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

Shinya Rai; Hirokazu Tanaka; J Luis Espinoza; Takahiro Kumode; Itaru Matsumura

doi:10.1016/j.lrr.2021.100256

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

Leuk Res Rep. 2021 Jun 12:15:100256. doi: 10.1016/j.lrr.2021.100256. eCollection 2021.

Authors

Shinya Rai¹, Hirokazu Tanaka¹, J Luis Espinoza¹, Takahiro Kumode¹, Itaru Matsumura¹

Affiliation

¹ Department of Hematology and Rheumatology, Kindai University Faculty of Medicine, Osaka-sayama, Osaka.

Abstract

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.

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

Publication types

Case Reports