2019 Fiscal Year Final Research Report
Metabolic reprogramming of leukemia stem cells by hematopoietic transcription factors
| Project/Area Number |
17K16192
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Hematology
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| Research Institution | Yokohama City University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 白血病幹細胞 / MLL白血病 / 細胞内代謝 / リプログラミング |
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| Outline of Final Research Achievements |
It has been reported that the function of leukemia stem cells (LSCs) is regulated by various factors such as transcription factors, epigenetic regulators and intracellular signaling. However, precise mechanism how these molecules regulate LSC function remains unclear. We herein examined a role of hematopoietic transcription factors in regulating self-renewal capacity of LSCs using MLL-ENL leukemia as a model. We found that PU.1 is absolutely required for LSC function of MLL leukemia. Transcriptome analysis revealed that PU.1 regulates various glycolytic enzymes, and loss of PU.1 leads to a global changes in metabolic landscape of LSCs.
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| Free Research Field |
血液学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、PU.1がMLL白血病のLSC制御において必須の役割を果たしていることが明らかとなった。さらにPU.1はLSCにおける代謝制御に重要な役割を果たしており、これによってLSCが維持されている可能性が明らかとなった。
以上の成果は、MLL白血病においてPU.1とその下流経路が治療の良い標的となることを示しており、将来的な新規治療薬開発に役立つものと期待される。
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