| Project/Area Number |
18591054
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Nagoya University |
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Principal Investigator |
KIYOI Hitoshi Nagoya University, Hospital, Associated Professor (90314004)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,920,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | leukemia / Nucleouhosmin / mutation / signal transduction |
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| Research Abstract |
Mutation of the nucleophosmin(NPMI) gene is found in about 30% of acute myeloid leukemia(AMC) patients, and is closely associated with the cemplete remission rate and a long-term survival rate. In addition, it has been reported that lower expression level of the NPM1 gene causes the development of myelodysplastic syndrome (MDS). Therefore, NPM seems to play an important role for the development and progression of AML and MDS. To date, several genetic alterations have been reportedly involved in the leukemogenesis. Importantly, the NPM1 gene mutation is closely asmciated with the FLT3 mutations. In this study we analyzed the molecular mechanism of mutant NPM for the development and progression of leukemia in the association with FLT3 gene mutations and found the following results.
1.We established the stably wild type or mutant NPM1-expressing 32D cell lines. Both cell lines did not show the 113 independent growth, and the proliferation rates were same.
2.Next we established the FLT3 and NPM1 coexpressing 32D cell lines. Mutant FLT3-expressing 32D cells showed IL3-independent growth, while additional expressing of wild type or mutant NPM1 did not affect the proliferation rate and G-CSF-induced differentiation.
3.However, growth inhibitory effects of several anti-leukemia agents and FLT3 kin ace inhibitors were lower in FLT3 and wild type NPM1-caexpressing 32D cells than FLT3 and mutant NPM1-coexpreccing cells.
4.Expression level of NPM1 mRNAis lower in the advanced stage MDS cells.
5.We generated wild type or mutant NPM specific antibodies. These antibodies can be used both in western blot and immunohistochemistry. By using these antibodies, we found mutant NPM exists in nucleus outside nucleoli as well as cytoplasma
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