translational research for novel therapy for leukemia utilizing microRNA expression analysis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08321
• 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: Kyoto University
• Principal Investigator: Hiramatsu Hidefumi 京都大学, 医学研究科, 講師 (40362503)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: マイクロRNA / 急性リンパ性白血病

Outline of Final Research Achievements

Based on the preceding data on microRNA expression of childhood acute lymphoblastic leukemia (ALL), we knocked down miR-146a of ALL cell lines using our lentivirus vector system. We found that the knockdown inhibited colony formation, which is mediated by the NOTCH pathway. However, the knocked-down cells did not show growth inhibition in the immune-compromised mouse model. Considering the possibility that a single miR does not significantly impact leukemic cell biology, we investigated not only miR but also mRNA expression of ALL patient samples by next-generation sequencing. By incorporating deposit data of pediatric ALL, we identified a novel miR signature（miR-low cluster； MLC）, which is associated with poor prognosis independently of unknown risk factors. Investigation on the molecular basis of MLC is underway.

Free Research Field

小児血液腫瘍

Academic Significance and Societal Importance of the Research Achievements

小児急性リンパ性白血病はリスクに応じた治療の層別化により予後の改善が見られてきた。先進国においては、90％以上の患者において長期生存が見られるようになってきたものの、未だ20％程度の患者は再発し、造血細胞移植を含む強力な治療が必要となる。さらなるリスク因子の探求は合併症なき治癒を目指す上で極めて重要である。本研究では、特定のマイクロRNA発現パターンが、従来のリクス因子とは独立した新たな因子になることを解明した点で極めて重要で、今後の診断治療の進歩が期待されるばかりでなく、分子学的背景の研究により新規治療法の開発に繋がりうる重要な成果と考えられる。