2021 Fiscal Year Final Research Report
Identification of human acute leukemia specific metabolic pathways
| Project/Area Number |
19H03687
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
赤司 浩一 九州大学, 医学研究院, 教授 (80380385)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 白血病幹細胞 / がん代謝 |
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| Outline of Final Research Achievements |
In the current study, we explored the critical metabolic mechanisms underlying the maintenance of stem cell properties in human acute leukemia. Through the analysis of metabolome data sets we have established, we found that human CD34+ acute leukemia cells exhibited significantly higher cellular content of branched chain amino acids (BCAAs) as compared to normal CD34+ hematopoietic stem progenitor cells. Inhibition of BCAA metabolism strongly impaired the maintenance of leukemic stem cell properties of human acute leukemia in the xenograft models. Furthermore, we explored the molecular machineries how BCAA metabolism regulate the stemness of human acute leukemia and demonstrated that BCAA metabolism is specifically required to maintain PRC2 components including EZH2 and EED. Thus, BCAA metabolism represents a specific regulator of stem cell properties via maintaining PRC2 function in human acute leukemia.
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| Free Research Field |
血液内科学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の遂行により、ヒト急性白血病における幹細胞性維持にとって重要な代謝特性としてBCAA代謝経路を同定することができた。また、BCAA代謝が利用する幹細胞性維持機構として、下流のPRC2機能制御を同定することができた。これらの結果から、BCAA代謝経路を標的としたヒト急性白血病における治療戦略を構築する上で、基盤的な特性を明らかにすることができた。したがって本研究の果たした意義は基礎的研究分野のみならず、今後の応用も含めた発展性のある内容であり、社会的意義も高いものであると考える。
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