Identification of regulator of differentiation of leukemia stem cell using genome editing system

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17824
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Kanazawa University
• Principal Investigator: kurayoshi kenta 金沢大学, がん進展制御研究所, 博士研究員 (00802901)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 分化 / 代謝

Outline of Final Research Achievements

Acute myeloid leukemia (AML) is malignant disease characterized by abnormal proliferation and differentiation blockade. We have found that metabolic reprograming including glycolysis are related with differentiation in the process of research into FOXO’s function. In this project, regulators of differentiation blockade are explored from FOXO target genes related with metabolism or all metabolic enzymes and transporters using CRISPR Cas9 screening. We have found that some metabolic enzymes play pivotal role in differentiation blockade. Moreover, the inhibitor represses proliferation of leukemia specifically.

Free Research Field

造血器腫瘍

Academic Significance and Societal Importance of the Research Achievements

すべての代謝酵素、トランスポーターを対象として未分化維持因子を網羅的に探索した結果、未分化維持に寄与する代謝酵素を複数同定した。本研究により、未分化維持に特に重要な経路及び代謝分子を特定することができ、代謝による未分化維持機構の一端が明らかとなった。また、代謝酵素の活性阻害は白血病特異的に抗増殖作用を示した。その研究成果は、将来、白血病患者に対して有用な治療薬の開発につながることが期待される。