Elucidation of the maintenance mechanism of leukemic stem cells in leukemia with high EVI1 expression and search for therapeutic target

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16299
• 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: Hino Toshiya 東京大学, 医学部附属病院, 助教 (20935746)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 急性骨髄性白血病 / EVI1 / 白血病幹細胞 / CRISPRスクリーニング

Outline of Final Research Achievements

High EVI1 expression is observed in approximately 5 to 10% of de novo acute myeloid leukemia, and this subgroup is known to have an extremely poor prognosis, but no effective treatment has been developed. In this study, in order to elucidate the mechanism by which EVI1 is involved in maintaining the stemness of leukemic stem cells, we integrated RNA sequence analysis and chromatin-immunoprecipitation sequence analysis using a leukemia mouse model with high EVI1 expression. We extracted candidate genes predicted to be regulated by EVI1 in leukemia stem cells. Knockout library screening was performed on these candidate genes to narrow down the genes necessary for maintaining leukemia stem cells, and 12 genes were extracted as candidates.

Free Research Field

血液・腫瘍内科

Academic Significance and Societal Importance of the Research Achievements

本研究ではEVI1高発現白血病マウスモデルを用いて、RNAシークエンス解析およびクロマチン免疫沈降シークエンス解析を統合的に解析し、さらに、in vivoでのノックアウトスクリーニングを行い、EVI1高発現白血病モデルマウスにおいて白血病幹細胞の維持に必要な遺伝子を抽出した。これらの遺伝子のEVI1高発現白血病における白血病幹細胞性維持機構を明らかにすることで、EVI1高発現白血病における新規治療を開拓できる可能性がある。