2017 Fiscal Year Final Research Report
Biological characterization of DDX41 germline and somatic mutations in myeloid neoplasms
| Project/Area Number |
16K19574
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Hematology
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| Research Institution | Kyoto University |
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Principal Investigator |
Kon Ayana 京都大学, 医学研究科, 特定助教 (20772403)
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| Research Collaborator |
OGAWA Seishi 京都大学, 大学院医学研究科, 教授 (60292900)
KOSEKI Haruhiko 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, チームリーダー (40225446)
NAKAYAMA Manabu 公益財団法人かずさDNA研究所, 先端研究開発部, 主任研究員 (30370927)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Keywords | 骨髄異形成症候群 / 急性骨髄性白血病 / 遺伝子改変マウス |
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| Outline of Final Research Achievements |
DDX41 is a newly identified leukemia predisposition gene encoding an RNA helicase, whose germline mutations are tightly associated with late-onset myeloid malignancies. In typical cases, a germline loss-of-function allele is compounded by a somatic missense mutation affecting the helicase domain in the remaining allele (p.R525H). To clarify the role of these DDX41 alleles, we generated Ddx41 heterozygous knock-out mice, as well as mice carrying the conditional R525H missense allele. In noncompetitive transplantation experiments, the recipient mice transplanted with Ddx41 R525H BM cells or Ddx41 heterozygous knock-out BM cells showed significant and progressive leukopenia compared with wild-type controls. Further, we identified several candidate targets of Ddx41 mutations through RNA sequencing of Ddx41 mutated hematopoietic stem and progenitor cells.
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| Free Research Field |
血液腫瘍病態学
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