Elucidation of mechanism of myeloproliferative neoplasm induced by abnormal DNA methylation

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17876
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Miyai Yurina (宮島優里奈) 国立研究開発法人理化学研究所, 生命医科学研究センター, 特別研究員 (70838218)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 骨髄増殖性腫瘍 / DNA脱メチル化

Outline of Final Research Achievements

In this study, we focused on the gene expression changes of progenitors in bone marrow leading to the onset of myeloproliferative neoplasms (MPN) and the cell dynamics after the development of MPN. We generated hematopoietic cell specific Tet2 deficient mice which show abnormal proliferation of myeloid cells and have symptoms of MPN and isolated each progenitor cells in bone marrow for transcriptome analysis. As a result of transcriptome analysis of progenitors from bone marrow of hematopoietic cell specific Tet2 deficient mice, we identified a novel group of progenitor cells which are expected to contribute to MPN pathogenesis. These cells show a characteristic pattern of surface markers that has not been reported previously and increase as aging. Furthermore, these cells have higher ability of proliferation and differentiation into myeloid cells compared to control mice. These results suggested that these progenitors are important cells which play a role in the MPN pathogenesis.

Free Research Field

血液および腫瘍内科学

Academic Significance and Societal Importance of the Research Achievements

本研究において、新たに見出した前駆細胞集団がMPNの発症に重要な役割を果たしている可能性が示唆された。MPN発症には、造血系前駆細胞における遺伝子の変異が重要であると考えられているが、発症に至るメカニズムは不明な点が多い。本研究では、その分子メカニズムの一端として骨髄系細胞への分化能が高い細胞集団を見出すことができた。今後、本細胞群の性質および病態への寄与を詳細に解析することで、MPNの治療に有用な新たな治療戦略の創出が期待できる。