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Development of novel diagnostics and treatments using HMGA2 mRNA in patients with myeloproliferative neoplasms

Research Project

Project/Area Number 15K09457
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Hematology
Research InstitutionFukushima Medical University

Principal Investigator

Harada-Shirado kayo  福島県立医科大学, 医学部, 助教 (00722521)

Co-Investigator(Kenkyū-buntansha) 小川 一英  福島県立医科大学, 医学部, 教授 (40423800)
池田 和彦  福島県立医科大学, 医学部, 准教授 (90381392)
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)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsHMGA2 / MPN / JAK2V617F / EZH2 / ASXL1 / 骨髄増殖性腫瘍 / Hmga2 / 骨髄線維症
Outline of Final Research Achievements

Myeloproliferative neoplasm (MPNs) are clonal haematological disorders. JAK2 V617F mutations lead to haematopoietic cell proliferation. High Mobility Group AT-hook 2 (HMGA2) is a non-histone chromatin protein, contributing to chromatin modification and epigenetic regulation. Previously, we showed that HMGA2 mRNA expression was frequently elevated in patients with MPNs, especially PMF. It may be progressing to AML and having difficulty to distinguish between PMF and secondary MF in patients with ET. Therefore, it is preferable to develop simple diagnostics and treatments using HMGA2 mRNA. We evaluated the impact of HMGA2 on MPNs by generated ⊿Hmga2/ JAK2V617F mice, which exhibited exacerbations disease(1). This study also showed most patients with PMF highly expressed HMGA2 mRNA with mutations in PRC2, EZH2 or ASXL1. These findings suggest the crucial role of HMGA2 with correlated to PRC2 in diagnostics and targets of treatment in patient with MPNs. (1)Ueda,et al, blood advances, 2017)

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (5 results)

All 2017 2016 2015

All Journal Article (4 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Hmga2 collaborates with JAK2 V617F in the development of myeloproliferative neoplasms2017

    • Author(s)
      Ueda K, Ikeda K, Ikezoe T, Harada-Shirado K, Ogawa K, Hashimoto Y, Sano T, Ohkawara H, Kimura S, Shichishima-Nakamura A, Nakamura Y, Shikama Y, Mori T, Mason PJ, Bessler M, Morishita S, Komatsu N, Shide K, Shimoda K, Koide S, Aoyama K, Oshima M, Iwama Aand Takeishi Y.
    • Journal Title

      Blood Advances

      Volume: 1 Issue: 15 Pages: 1001-1015

    • DOI

      10.1182/bloodadvances.2017004457

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular response of e19a2 BCR-ABL1 chronic myeloid leukemia with double Philadelphia chromosome by dasatinib.2016

    • Author(s)
      Ikeda K, Harada-Shirado K, Matsumoto H, Noji H, Ogawa K, Takeishi Y.
    • Journal Title

      Clin Oncol

      Volume: 4(14)

    • Related Report
      2015 Research-status Report
  • [Journal Article] Dysregulation of the MIRLET7/HMGA2 axis with methylation of the CDKN2A promoter in myeloproliferative neoplasms. .2015

    • Author(s)
      Harada-Shirado K, Ikeda K*, Ogawa K, Ohkawara H, Kimura H, Kai T, Noji H, Morishita S, Komatsu N, Takeishi Y.
    • Journal Title

      Brit J Haematol

      Volume: 168(3) Pages: 338-49

    • Related Report
      2015 Research-status Report
  • [Journal Article] Impact of red blood cell and platelet transfusions on allogeneic hematopoietic stem cell transplantation.2015

    • Author(s)
      Mashimo Y, Ikeda K*, Ohkawara H, Takahashi H, Shichishima-Nakamura A, Harada-Shirado K, Furukawa M, Sukegawa M, Saito S, Noji H, Ogawa K, Ohto H, Takeishi Y.
    • Journal Title

      ISBT Scientific series.

      Volume: 10(2) Pages: 93-99

    • Related Report
      2015 Research-status Report
  • [Presentation] HMGA2 orchestrates the tumorgenesis of myeloproliferative neoplasms (MPN) in corporation with JAK2V617F.2016

    • Author(s)
      Ueda K, Ikeda K, Ikezoe T, Ogawa K, Harada-Shirado K, Ohkawara H, Komatsu N, Shimoda K, Koide S, Oshima M, Iwama A, Takeishi Y.
    • Organizer
      American Society of Hematology
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2016-12-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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