Development of a novel therapy targeting alteration of lipid metabolism in leukemia

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17369
• 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: The University of Tokyo
• Principal Investigator: Mizuno Hideaki 東京大学, 医学部附属病院, 助教 (70869594)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 急性骨髄性白血病 / 脂質代謝

Outline of Final Research Achievements

It is becoming clear that unique metabolic patterns created by alterations in key intracellular metabolic pathways such as glucose and amino acid metabolism in leukemia are involved in leukemia stemness and chemotherapy resistance. On the other hand, vulnerabilities generated by these metabolic alteration can be novel therapeutic targets. This study aims to establish a novel therapy by targeting lipid metabolism in leukemia. We have shown that several genes involved in cholesterol metabolism are aberrantly expressed in leukemia cells. In this study, we evaluated the effects of inhibiting these genes and metabolic pathways.

Free Research Field

造血器腫瘍

Academic Significance and Societal Importance of the Research Achievements

難治性白血病であるEVI1高発現白血病マウスモデル、公開データベースによる急性骨髄性白血病患者のmRNAと予後の解析、治療抵抗性急性骨髄性白血病患者検体の単一細胞トランスクリプトーム解析のそれぞれから、脂質代謝経路の遺伝子発現異常が治療抵抗性に関与していると考えられる結果が得られた。これらの代謝経路の主要細胞における機能的な探索を今後継続して行う必要があるが、難治性白血病の新規治療法開発につながる成果が得られた。