2014 Fiscal Year Final Research Report
Analysis of ligand dependent resistance mechanism of RTK inhibitors
Project/Area Number |
24591387
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Hematology
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Research Institution | Nagoya University |
Principal Investigator |
KIYOI Hitoshi 名古屋大学, 医学(系)研究科(研究院), 教授 (90314004)
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Project Period (FY) |
2012-04-01 – 2015-03-31
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Keywords | 血液腫瘍学 / チロシンキナーゼ / 分子標的療法 / 白血病 |
Outline of Final Research Achievements |
In this study, I analyzed the FLT3 ligand (FL)-dependent resistance mechanism of FLT3 inhibitors using wild type FLT3 (Wt-FLT3) and FLT3-ITD or extracellular domain-lacked FLT3-ITD (cyFLT3-ITD) co-expressing cells. I demonstrated that FL-stimulation activates co-expressing-Wt-FLT3 and MAPK, resulting in the reduction of anti-leukemia activity of FLT3 inhibitor. This FL-dependent inhibitory effect of FLT3 inhibitors was also confirmed in the human leukemia cell xenotransplant mouse models, in which Wt-FLT3 and FLT3-ITD co-expressing leukemia cells were not sufficiently eradicated by FLT3 inhibitors. These results also indicate that Wt-FLT3 expression level is a molecular marker for predicting the efficacy of FLT3 inhibitors.
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Free Research Field |
血液内科学
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