2015 Fiscal Year Final Research Report
Novel therapeutic approaches targeting intracellular trafficking of RTK mutants in acute myeloid leukemia cells.
| Project/Area Number |
25461439
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kinki University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMURA Itaru 近畿大学, 医学部, 教授 (00294083)
HIRASE Chikara 近畿大学, 医学部, 医学部講師 (30548590)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | 白血病 / 受容体 / 細胞内輸送 / 分子標的 |
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| Outline of Final Research Achievements |
FLT3-ITD and KIT D816V mutation are frequently found in AML and associated with poor prognosis. In this study, we evaluated the anti-leukemic effects of an inhibitor of membrane trafficking, chlorpromazine (CPZ).
Recent studies demonstrated that these oncogenic RTKs are mislocalized in the cytoplasm, where they transmit aberrant signals to downstream. CPZ disrupted the intracellular trafficking of RTK mutants, and significantly suppressed activities of RTK mutants and their downstream molecules. Consequently, CPZ inhibited the growth and survival of AML cells with mutant RTK in a dose-dependent manner. In xenotransplantation models, administration of CPZ significantly reduced engraftment of AML cells, and also showed the cytotoxic effect to AML stem cells, while displaying minimal toxicity to normal hematopoietic cells. These results suggest that CPZ would be a promising therapeutic drug to eradicate AML cells with an established safety profile.
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| Free Research Field |
血液内科学
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