Elucidation of the undifferentiated maintenance mechanism of leukemia stem cells regulated by the lysosomal metabolic pathway

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16264
• 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): 2021-04-01 – 2023-03-31
• Keywords: 代謝

Outline of Final Research Achievements

The applicant discovered the potential of lysosomes to enhance the expression of oncogenes and maintain the undifferentiated state in leukemia stem cells by maintaining iron homeostasis. In this study, we aimed to analyze the mechanism of undifferentiated maintenance in leukemia stem cells by: 1) identifying the regulatory mechanism of oncogenes expression through lysosomal iron metabolism, and 2) exploring downstream undifferentiated maintenance factors of lysosomes and iron. It was revealed that lysosomes control the expression of oncogenes by inducing iron-dependent enhancer reprogramming. Additionally, iron-binding proteins contributing to undifferentiated maintenance and enhancer control of oncogene was identified. Therefore, a portion of the undifferentiated maintenance mechanism mediated by lysosomal iron metabolism has been elucidated.

Free Research Field

血液がん

Academic Significance and Societal Importance of the Research Achievements

本研究により、リソソーム-鉄経路が、がん遺伝子のエンハンサーリプログラミングを誘導することで、白血病細胞の未分化性維持に寄与することが判明した。本研究により、リソソームを介したがんの悪性形質の制御機構が明らかとなった。本研究成果は、あらたながん治療戦略の構築につながる可能性がある。