Epigenomic analysis in refractory AML

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08350
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Yokohama City University
• Principal Investigator: SHIBA Norio 横浜市立大学, 附属病院, 講師 (50600615)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 急性骨髄性白血病

Outline of Final Research Achievements

CHIP-seq was performed using a sample with acute myeloid leukemia harboring NUP98-NSD1 with high expression of PRDM16. As a result, some novel candidate genes were identified, in addition to known cancer-related genes such as SKI and RUNX1. ATAC-seq found that the promoter region of PRDM16 is open in the AML samples showing PRDM16 high expression. Intriguingly, same region showed low DNA methylation pattern, although gene body of PRDM16 gene itself was highly methylated resulting in inhibiting binding with Polycomb complex. These alteration contributes to the refractory AML. Furthermore, microRNA sequences were performed on 48 pediatric AMLs with carrying various genetic backgrounds. They classified them into four clusters based on expression patterns, some of which correlated with existing genetic abnormalities.

Free Research Field

白血病

Academic Significance and Societal Importance of the Research Achievements

難治AML症例より同定された遺伝子異常の機能的な意義を解明することで、AMLの発症原因を解明し、創薬開発に繋げていくことで難治AML患者を救命することが可能となる。層別化については、これまでの解析にて概ね完了している。しかしながら、まだ約10％の患者においては、driverとなる遺伝子異常を見いだすことが出来ていない（これらの症例の多くは複雑な染色体の構造異常を認め、予後不良である）。よって、より高精度の治療層別化フローチャートを作成し、すべての小児AML症例の再発リスク、予後予測に基づいた適切な治療強度を選択できるようにするため、これらの10％の症例の発病原因を探索することに注力する。