| Project/Area Number |
18K16100
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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 | Japanese Foundation for Cancer Research |
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Principal Investigator |
Sunami Yoshitaka 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 (50732864)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 急性骨髄性白血病(AML) / 骨髄生着 / Hoxa9 / Meis1 / Sytl1 / shRNAスクリーニング / 急性骨髄性白血病 / エクソソーム / 骨髄微小環境 |
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| Outline of Final Research Achievements |
Synaptotagmin-like 1 (Sytl1, also known as Slp1) was identified as a target gene of Meis1, a transcriptional factor which plays a critical role in AML development. In this project, we attempted to clarify the model that Sytl1 regulated the secretion of exosomes, and subsequently promotes the engraftment of AML cells into the bone marrow. However, the experiment using Slp1-knock out mouse revealed that the function of Sytl1 in the engraftment of AML cells was limited in non-Meis1 associated AML. Therefore, to identify the critical factor for the AML cell engraftment, we performed a whole-genome lentiviral shRNA screening followed by the second screening using custom made sgRNA libraries. Finally, we identified 37 candidate genes that could be associated with the engraftment of AML cells.
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| Academic Significance and Societal Importance of the Research Achievements |
AMLは高率に再発し、その原因として骨髄定着したAML細胞が治療後も残存することが挙げられるが、AML細胞が骨髄定着する分子基盤は明らかでない。本研究で同定した標的候補遺伝子はAML細胞の骨髄定着に重要な役割を果たしている可能性があり、したがって本研究成果は学術的に意義がある。また、これらの遺伝子を標的とした新規治療法を開発することで、治療後のAML残存病変を駆逐し、AML再発や治療抵抗性獲得を克服することが期待できる。さらには同定した遺伝子を特異的な治療標的とすることで、大きな副作用のない再発予防が実現でき、AML患者のQOLを改善することが可能となるため、本研究成果の社会的意義も高い。
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