Molecular basis of MDS pathogenesis and construction of novel MDS prognostic model

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08366
• 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: The University of Tokyo
• Principal Investigator: Oshima Motohiko 東京大学, 医科学研究所, 講師 (70506287)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: MDS / ATAC-seq / 転写因子 / 造血器腫瘍

Outline of Final Research Achievements

ATAC-seq analysis of MDS using stem and progenitor fraction revealed that, differentially accessible regions (DARs) in MDS include large amount of normal differentiation-related regions. We also found the transcription factor networks that strongly related to the prognosis and stratified MDS based on the transcription factor network abnormality in MDS stem and progenitor cells. These characteristic features were not clearly observed in the gene expression profiles from same samples, showing that these finding are the first to be revealed by focusing on chromatin characteristics.

Free Research Field

幹細胞分子医学、血液学

Academic Significance and Societal Importance of the Research Achievements

MDS幹細胞および前駆細胞分画を用いたクロマチン特性解析により、予後に関わる転写因子ネットワークを同定するとともに、転写因子ネットワーク変動に基づく新規のMDSサブグループが存在する事を明らかにした。今後、遺伝子変異との関わりや転写因子の標的遺伝子群などについてさらに詳細に検証を行うことで、新たなMDS病態の分子基盤を構築し、より適切な治療選択や新規治療法の開発に繋げる事が期待される。