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

• Project/Area Number: 15K09457
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Fukushima 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: ¥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)
• Keywords: HMGA2 / 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)

Research Products

• [Journal Article] Hmga2 collaborates with JAK2 V617F in the development of myeloproliferative neoplasms (2017)
  • 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
  • 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)
• [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
• [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
• [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
  • Int'l Joint Research