Development of novel anti-leukemic therapy targeting clathrin-dependent endocytosis

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09461
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kindai University
• Principal Investigator: MATSUMURA Itaru 近畿大学, 医学部, 教授 (00294083)
• Co-Investigator(Kenkyū-buntansha): 平瀬 主税 近畿大学, 医学部, 講師 (30548590) ; 田中 宏和 近畿大学, 医学部, 講師 (40360846) ; 森田 泰慶 近畿大学, 医学部, 講師 (80411594)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 白血病 / 阻害薬 / 分子標的

Outline of Final Research Achievements

We here show that pharmacologic inhibition of clathrin-dependent trafficking of mutated receptor tyrosine kinases (mtRTK such as FLT3-ITS and KIT D814V mutation) with chlorpromazine (CPZ) disrupts their cellular localization and inhibits their activities. CPZ suppressed the growth of primary AML cells with mtRTK, including CD34+38- AML stem cells in vitro. In mice transplanted with primary AML cells, administration of CPZ at a clinically relevant concentration inhibited the growth of AML cells with mtRTK while it showed a marginal effect on the growth of AML cells with wild-type RTK. Also, CPZ treatment eliminated AML stem cells at the periosteal region in the bone marrow of the recipient mice. These results demonstrate that the intracellular trafficking of mtRTKs would be a good therapeutic target and CPZ would be new therapeutic agent against AML with mtRTK.

Free Research Field

血液内科学