Downstream targets of the leukemia-associated gene EVI1 in normal hematopoiesis

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22934
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0904:Internal medicine of the bio-information integration and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Chiba AKira 東京大学, 医学部附属病院, 助教 (70875947)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 正常造血 / 急性骨髄性白血病

Outline of Final Research Achievements

ChIP-seq was performed on the genetically engineered cell lines and integrated with RNA-seq data from Evi1 knockout cell lines and ChIP-seq data from Evi1-overexpressing mouse leukemia cells to obtain candidate genes involved in maintaining undifferentiated HSCs in cooperation with Evi1. Of these, overexpression of Gfi1 in HSCs from mice lacking Evi1 restored colony-forming ability. In addition, overexpression of Gfi1 rescued Evi1 deletion using a competitive transplantation system in mice. These findings suggest that Gfi1 is a downstream target of Evi1 in normal hematopoietic models and may cooperate with Evi1 to maintain stemness.

Free Research Field

急性骨髄性白血病

Academic Significance and Societal Importance of the Research Achievements

本研究は正常造血幹細胞に発現する遺伝子が高発現することによって特徴づけられるタイプの、他の難治性急性骨髄性白血病（AML）に共通する治療開発のモデルとなりうる可能性があり、これによって難治性AMLの病態解明と新規治療開発の基盤を確立することができる。