| Project/Area Number |
23240125
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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 |
Carcinogenesis
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| Research Institution | Japanese Foundation for Cancer Research |
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Principal Investigator |
NAKAMURA Takuro 公益財団法人がん研究会, がん研究所発がん研究部, 部長 (00180373)
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| Co-Investigator(Kenkyū-buntansha) |
YOKOYAMA Takashi 公益財団法人がん研究会, がん研究所発がん研究部, 研究員 (00535833)
中武 真由香 公益財団法人がん研究会, がん研究所発がん研究部, 研究員 (40432041)
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| Co-Investigator(Renkei-kenkyūsha) |
GOITSUKA Ryo 東京理科大学, 生命科学研究所, 教授 (50301552)
ITO Etsuro 弘前大学, 大学院医学系研究科, 教授 (20168339)
HAYASHI Yasuhide 群馬県小児医療センター, センター長 (30238133)
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| Project Period (FY) |
2011-11-18 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥24,440,000 (Direct Cost: ¥18,800,000、Indirect Cost: ¥5,640,000)
Fiscal Year 2013: ¥12,220,000 (Direct Cost: ¥9,400,000、Indirect Cost: ¥2,820,000)
Fiscal Year 2012: ¥12,220,000 (Direct Cost: ¥9,400,000、Indirect Cost: ¥2,820,000)
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| Keywords | 骨髄性白血病 / 実験動物モデル / 遺伝子経路 / 転写制御 / シグナリング / 急性骨髄性白血病 / Hoxa9 / Meis1 / Sytl1 / 骨髄ニッチ / ノックアウトマウス / FLT3 / CXCR4 / Smad7 / Trib1 / Bcl11a / ChIP-Seq |
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| Research Abstract |
We have analyzed the molecular network around Hoxa9 and Meis1 that play a important role as transcription factors in development of acute myeloid leukemia (AML). Meis1 is required for engraftment of leukemic cells in bone marrow niche. ChIP-Seq analysis and gene expression profiling identified the Meis1 target gene Sytl1 that is responsible for Meis1's function. Sytl1 facilitates intracellular trafficking of membrane-bound receptors to modulate cell-cell interaction between leukemic cells and bone marrow stroma. Trib1 downregulates the C/EBPa protein and regulates granulocytic differentiation. Trib1 somatic mutation was identified in a case of human AML. Retroviral tagging experiments identified Bcl11a as a novel cooperative gene for Trib1 in leukemogenesis.
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