| Project/Area Number |
22K16299
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Hino Toshiya 東京大学, 医学部附属病院, 助教 (20935746)
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| Project Period (FY) |
2022-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2022: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 急性骨髄性白血病 / EVI1 / 白血病幹細胞 / CRISPRスクリーニング / 急性白血病 / 白血病 / 幹細胞 |
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| Outline of Research at the Start |
急性骨髄性白血病(AML)の中でEcotropic viral integration site 1 (EVI1)高発現はde novo AMLの約5~10%程度に認められ、予後不良因子として知られるが、近年の分子標的治療の進歩にもかかわらず有効な治療法が開発されていない。本研究では、EVI1高発現白血病マウスモデルを用いて、EVI1の白血病幹細胞性の維持に関わる分子学的機序を明らかにすることで、新しい治療標的薬を開発することを目的とする。
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| Outline of Final Research Achievements |
High EVI1 expression is observed in approximately 5 to 10% of de novo acute myeloid leukemia, and this subgroup is known to have an extremely poor prognosis, but no effective treatment has been developed. In this study, in order to elucidate the mechanism by which EVI1 is involved in maintaining the stemness of leukemic stem cells, we integrated RNA sequence analysis and chromatin-immunoprecipitation sequence analysis using a leukemia mouse model with high EVI1 expression. We extracted candidate genes predicted to be regulated by EVI1 in leukemia stem cells. Knockout library screening was performed on these candidate genes to narrow down the genes necessary for maintaining leukemia stem cells, and 12 genes were extracted as candidates.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究ではEVI1高発現白血病マウスモデルを用いて、RNAシークエンス解析およびクロマチン免疫沈降シークエンス解析を統合的に解析し、さらに、in vivoでのノックアウトスクリーニングを行い、EVI1高発現白血病モデルマウスにおいて白血病幹細胞の維持に必要な遺伝子を抽出した。これらの遺伝子のEVI1高発現白血病における白血病幹細胞性維持機構を明らかにすることで、EVI1高発現白血病における新規治療を開拓できる可能性がある。
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