| Project/Area Number |
15K09484
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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 | Fukushima Medical University |
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Principal Investigator |
Ikeda Kazuhiko 福島県立医科大学, 医学部, 准教授 (90381392)
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| Co-Investigator(Kenkyū-buntansha) |
小川 一英 福島県立医科大学, 医学部, 教授 (40423800)
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| Co-Investigator(Renkei-kenkyūsha) |
Ueda Koki 福島県立医科大学, 医学部 血液内科学講座, 助教 (80632190)
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | MPN / microRNA / histone / EZH2 / 骨髄増殖性腫瘍 / HMGA2 / let-7 / ポリコーム / 骨髄線維症 |
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| Outline of Final Research Achievements |
Myeloproliferative neoplasms (MPNs) are characterized by activation of JAK-STAT pathway due to driver mutations including JAK2V617F, but some additional abnormalities may be necessary to maintain an MPN clone and advance the disease. The HMGA2, which acts as an oncogene by regulating expression of various genes, is frequently overexpressed due to downregulation of let-7 microRNAs and/or mutations in EZH2 in advanced MPN such as myelofibrosis. In mice with JAK2V617F, deletion of Ezh2 upregulates Hmga2. Correspondingly, overexpression of Hmga2 enhances splenomegaly and deteriorate anemia in mice carrying JAK2V617F, mimicking severe MPN. Therefore, Hmga2 may play an important role in progression of MPN.
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