Integrative understanding of the functional role of DNA demethylation-associated molecule in the process of leukemic initiation

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08352
• 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: Mie University
• Principal Investigator: Ono Ryoichi 三重大学, 医学系研究科, 准教授 (40422414)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 造血器腫瘍

Outline of Final Research Achievements

In this study, we focused on the epigenetic mechanism controlling gene expression, which has been reported to play an important role in the molecular mechanism of oncogenesis including leukemogenesis, and performed various molecular biological analyses using several leukemia mouse model systems. Consequently, it was suggested that ablation of one of DNA demethylation-associated molecules contributed to the development of acute promyelocytic leukemia in an in vitro model system. On the other hand, in acute myeloid leukemia, ablation of the above molecule did not affect the main molecular pathogenesis. It is considered that we have found a part of the complexity of the functional aspects of epigenetic regulatory molecules, and we are planing to do further detailed analysis.

Free Research Field

血液腫瘍学

Academic Significance and Societal Importance of the Research Achievements

白血病は、血液の「がん」であり、強力な治療法が開発された今日においても、根治が困難なケースが存在する。そうした場合の切り札の一つが、白血病細胞に非常に特徴的な性質を攻撃する分子標的療法である。本研究では、近年白血病の発症に重要な役割を担うことが判明してきた、ゲノムDNAの化学的修飾の一つ、メチル化に関連した解析を行い、ある種の白血病では、そうしたメチル化を取り除く分子が白血病発症に一定の寄与をしているようであるが、別のタイプではしてないと考えられ、この種の分子を分子標的とするには、さらなる詳細な解析を要すると考えられた。