| Project/Area Number |
15K09482
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
佐藤 勉 札幌医科大学, 医学部, 講師 (40404602)
堀口 拓人 札幌医科大学, 医学部, 研究員 (70634674)
高田 弘一 札幌医科大学, 医学部, 講師 (90398321)
村瀬 和幸 札幌医科大学, 医学部, 講師 (90444918)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | エクソソーム / マイクロRNA / 白血病 / 骨髄異形成症候群 / 骨髄間質細胞 / PCBP1 / エキソソーム / 間葉系幹細胞 / 骨髄間質 / 白血病幹細胞 / 細胞外小胞 |
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| Outline of Final Research Achievements |
The failure of normal hematopoiesis is observed in myeloid neoplasms. However, the precise mechanisms governing replacement of normal hematopoietic stem cells in their niche by myeloid neoplasm stem cells have not been clarified yet. Primary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) cells induced aberrant expression of multiple hematopoietic factors including JAG1, SCF and ANGPT1 in mesenchymal stem cells. Importantly, transfer of myeloid neoplasm-derived extracellular vesicles reduced the hematopoietic-supportive capacity of mesenchymal stem cells. Analysis of exosomal microRNA indicated that several species including miR-7977 from acute myeloid leukemia cells were higher than those from normal CD34+ cells. Remarkably, the copy number of miR-7977 in BM interstitial fluid was elevated in not only AML, but also MDS, as compared with control bone marrow. Thus, miR-7977 in extracellular vesicles may be a critical factor that induces failure of normal hematopoiesis.
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