| Project/Area Number |
24591405
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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) |
TAKEISHI Yasuchika 福島県立医科大学, 医学部, 教授 (40272067)
OGAWA Kazuei 福島県立医科大学, 医学部, 教授 (40423800)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 骨髄増殖性腫瘍 / 原発性骨髄線維症 / HMGA2 / マイクロRNA / エピジェネティックス / HMGA2高発現 / DNAメチル化 / 病態進展 / 国際情報交換 / 骨髄性腫瘍 |
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| Outline of Final Research Achievements |
Myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia and primary myelofibrosis (PMF), are clonal hematological disorders characterized by proliferation of mature blood cells. In this study, we found deregulated HMGA2 mRNA expression due to reduced let-7 micro RNA (miRNAs) in granulocytes from patients with almost all of PMF and over 20% of PV and ET, being associated with splenomegaly, elevated serum LDH values, and methylation of p16 promoter. Since association of histone deacetylase (HDAC) with HMGA2 has been reported in cord blood-derived cells, we next studied effects of an HDAC inhibitor panobinostat on expressions of HMGA2 and let-7 in HMGA2-expressing myeloid cells including PMF-derived CD34+ cells. The panobinostat decreased expression of HMGA2 through 3’UTR of HMGA2 mRNA by increasing expressions of let-7 miRNAs. Thus, deregulated expression of HMGA2 due to downregulation of let-7 miRNAs is a possible therapeutic target of HDACi in MPNs.
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