| Project/Area Number |
16K10026
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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 |
Pediatrics
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| Research Institution | Kyoto University |
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Principal Investigator |
Niwa Akira 京都大学, iPS細胞研究所, 特定拠点助教 (20546999)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 白血病 / iPS細胞 / 疾患モデル / 白血病モデル / クローン進化 / 癌 / 遺伝子 / シグナル伝達 / 発現制御 |
|---|
| Outline of Final Research Achievements |
Onset of acute myeloid leukemia (AML) has been accounted for by cooperation between multiple genetic alterations which induce abnormal control of various cellular pathways. Among the previously listed leukemogenic lesions, AML1-ETO fusion (AE) generated by translocation (8;21) (q22;q22) is one of the common mutations observed in 20-40% of patients. AE affects transcriptional regulation associated with hematopoietic differentiation, while 60% of AE-positive AML cases are shown to have together other types of mutation of genes involved in cell proliferation. However, the detailed mechanisms of how they work in the very early stages of leukemogenesis and what unknown “cooperative ” cues function in those periods. From this viewpoint, in order to identify novel cellular molecules involved in the acquisition of leukemic phenotypes, we have conducted the gene-trap strategy-based phenomic screen in the use of pluripotent stem cell (PSC)-derived hematopoietic culture.
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| Academic Significance and Societal Importance of the Research Achievements |
これまでのAML 研究では新たな変異を探索同定し、その機能を解析する手法が多数であった。本研究により、発症後のクローン進化 で見出される変異獲得機序には先行する白血病遺伝子の発現、および病態に関連した炎症シグナルに媒介される無い税制変異誘導遺伝子の働きが関与していることが示唆された。今後、AML発症段階の細胞での特異的 APOBEC 関与および変異獲得機構をより詳細に明らかすることができれば、腫瘍研究全体に新たな一石を投じる成果となる。
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