Analysis of hematopoietic regulation mechanisms by a novel repressor for RUNX1

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09936
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: YOSHIDA TATSUSHI 京都府立医科大学, 医学(系)研究科(研究院), 講師 (80315936)
• Co-Investigator(Kenkyū-buntansha): 奥田 司 京都府立医科大学, 医学(系)研究科(研究院), 教授 (30291587)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: RUNX1 / 白血病 / 造血 / 転写因子

Outline of Final Research Achievements

RUNX1 gene is frequently point mutated or chromosomal translocated in acute leukemia and myelodisplasia. RUNX1 is essential for definitive hematopoiesis in fatal liver and plays a role in hematopoietic development in adult. RUNX1 acts as a transcription factor and regulates gene expression related to hematopoiesis, however regulation of RUNX1 itself has not been elucidated fully. Thus, we identified CRP1, a novel binding factor of RUNX1 and found that it repressed transcriptional regulation by RUNX1. In this research project, we analyzed the mechanism in which CRP1 affected to RUNX1 function and the effect of CRP1 on hematopoiesis regulated by RUNX1 in gene-modified mice. In addition we performed an establishment of a screening system to search compounds which can block the interaction between RUNX1 and CRP1.

Free Research Field

造血腫瘍学

Academic Significance and Societal Importance of the Research Achievements

RUNX1は白血病発症や造血分化異常と関連する因子であるが、RUNX1の機能を調節する効果的な手法は今まで報告されていなかった。本研究では、新たなRUNX1結合因子を発見し、そしてその因子がRUNX1機能に及ぼす影響を解析した。この因子とRUNX1との相互作用を標的とすることによって、RUNX1の機能不全を回復することができ、将来的には白血病や造血異常の改善に結び付くことが示唆された。したがって、本研究成果は十分な学術的意義および社会的意義を有していると考えられた。