| Project/Area Number |
20249051
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | The University of Tokyo |
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Principal Investigator |
KITAMURA Toshio The University of Tokyo, 医科学研究所, 教授 (20282527)
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| Co-Investigator(Kenkyū-buntansha) |
KITAURA Jiro 東京大学, 医科学研究所, 助教 (30282651)
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| Co-Investigator(Renkei-kenkyūsha) |
YUJI Koichiro 東京大学, 医科学研究所, 助教 (50396868)
TOJO Arinobu 東京大学, 医科学研究所, 教授 (00211681)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥48,620,000 (Direct Cost: ¥37,400,000、Indirect Cost: ¥11,220,000)
Fiscal Year 2010: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
Fiscal Year 2009: ¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
Fiscal Year 2008: ¥20,540,000 (Direct Cost: ¥15,800,000、Indirect Cost: ¥4,740,000)
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| Keywords | 発現クローニング / レトロウィルスベクター / AML1 / MDS / 遺伝子変異 / レトロウイルスベクター / レトロゥィルスベクター |
|---|
| Research Abstract |
We studied the molecular mechanisms of etiology of leukemia, myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) mainly through the usage of mouse bone marrow transplant (BMT) model. Mutations involved in leukemogenesis are classified into two major groups : class I mutations induced proliferation or block apoptosis while class II mutations hamper differentiation of hemopoietic cells. In this research project, we have shown using a mouse BMT model that class I mutations induce MPN, that class II mutations induce MDS and that combination of class I and class II mutations induce acute leukemia. We have also indicated that additional class I mutations such as FLT3-ITD or overexpression of Evi1 could lead to progression of MDS to overt leukemia and that additional class mutations such as overexpression of Hes1 could result in progression of MPN to acute leukemia, blast crisis of CML. Thus, the combinations of mutations and the timing of each mutation will determine the disease course of MDS/overt leukemia, MPN/overt leukemia and acute leukemia.
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