Search for novel intervention methods for hematopoietic transcription control and research for its clinical application

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08846
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Okuda Tsukasa 京都府立医科大学, 医学(系)研究科(研究院), 教授 (30291587)
• Co-Investigator(Kenkyū-buntansha): 桑原 康通 京都府立医科大学, 医学(系)研究科(研究院), 講師 (30590327) ; 吉田 達士 京都府立医科大学, 医学(系)研究科(研究院), 講師 (80315936)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 造血器腫瘍 / 転写制御 / 染色体転座 / RUNX1 / AML1 / 分子標的薬 / Yeast Two-Hybrid / 遺伝子改変マウス

Outline of Final Research Achievements

RUNX1 is a transcription factor that plays important roles in the development and differentiation of hematopoietic cells, and its genetic alteration is frequently involved in the development of human leukemia. In this study, we performed a multifaceted analysis to look into the molecular mechanism of RUNX1 function. As a result, (1) several amino acid residues targeted for post-translational modification, which are important for the biological action of RUNX1, were identified. (2) New inhibitory factor and novel activator that interact with RUNX1 were identified and now are under investigation. (3) New cell lines were established that should serve as the useful tools for further analysis of the interplay of RUNX1 and SNF5. (4) We found TRAIL and C11orf21 as novel target genes that are transcriptionally regulated by RUNX1.

Free Research Field

腫瘍生化学

Academic Significance and Societal Importance of the Research Achievements

RUNX1は造血関連転写因子であり、これまでの多くの先行研究からは、この分子の機能不全が高頻度にヒト白血病の発症に関与していることが明らかにされている。明らかにRUNX1は次世代の新規白血病予防・治療薬や造血細胞制御薬などの開発における新規標的分子と見なされているものの、その機能の詳細が不明なことが、開発上の隘路となっていた。本研究によって新規に見いだされた知見はRUNX1の作用メカニズム・調節メカニズムの理解を多面的に進める意義があるものと考えている。こうした研究の延長上に新たな造血器疾患克服への道筋が見いだされるものと期待される。