2021 Fiscal Year Final Research Report
Analysis of familial platelet disorder based on the novel function of RUNX1
Project/Area Number |
19K08852
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 54010:Hematology and medical oncology-related
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Research Institution | Institute of Physical and Chemical Research |
Principal Investigator |
SUZUKI TAKAHIRO 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, 上級研究員 (00553661)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | 家族性血小板異常症 / DNAメチル化 |
Outline of Final Research Achievements |
Familial platelet dyscrasia (FPD) is an inherited hematologic disorder characterized by platelet abnormalities and high incidence of myeloid malignancies. The aim of this study was to identify DNA methylation abnormalities in FPD. Three FPD model iPS cell lines were established by CRISPR/Cas9 system and induced to differentiate into hematopoietic progenitor cells and megakaryocytes in vitro. We also identified abnormal DNA methylation in hematopoietic progenitor cells and found that ETS family transcription factor binding motifs were enriched in the hypermethylation sites. This suggests that ETS family transcription factors induce DNA methylation abnormalities in FPD.
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Free Research Field |
ゲノム科学
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Academic Significance and Societal Importance of the Research Achievements |
本研究はこれまで知られていなかった家族性血小板異常症のDNAメチル化異常を明らかにした新規性の高い研究成果である。ま家族性血小板異常症は高率に骨髄性悪性腫瘍を発症することから"前がん状態"にあると考えることができる。実際に家族性血小板異常症の原因遺伝子RUNX1は突発性の骨髄性悪性腫瘍においても高い確率で変異がみられる。このことから、本研究で明らかとなった家族性血小板異常症でのDNAメチル化異常は家族性血小板異常症自体の理解を深めるとともに、骨髄性悪性腫瘍の発症メカニズムについても重要な知見を与えるものである。
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