The role of HMGA2 in the pathogenesis of MPN

• Project/Area Number: 16K19582
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Fukushima Medical University
• Principal Investigator: UEDA KOKI 福島県立医科大学, 医学部, 助教 (80632190)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 骨髄増殖性腫瘍 / HMGA2

Outline of Final Research Achievements

MPN are driven by mutations in JAK2, CALR and MPL.We have recently shown high HMGA2 mRNA level in almost all patients with myelofibrosis. Thus, to clarify if HMGA2 affect JAK2V617F+ hematopoiesis, we crossed HMGA2-overexpressing mice with JAK2V617F Tg mice. At 3 months old, leukocytosis, thrombocytosis, anemia and splenomegaly were most severe in double-Tg. Hmga2 and JAK2VF Tg mouse survived for over a year, but all double-Tg died within 5 months. Lineage-Sca1+Kit+ cells were most frequent in double-Tg followed by ∆Hmga2, indicating HMGA2 contributes to expansion of JAK2V617F+ hematopoietic stem cells (HSC). In competitive/serial transplants, ∆Hmga2 and double-Tg cells steadily expanded, while JAK2VF cells were decreased and eventually rejected in 3rd transplant. Thus, HMGA2 may accelerate proliferative hematopoiesis harboring JAK2V617F with expanding MPN HSC.

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
• [Presentation] HMGA2 Orchestrates the Tumorgenesis of Myeloproliferative Neoplasms (MPN) in Corporation with JAK2V617F (2016)
  • Author(s): Koki Ueda, Kazuhiko Ikeda, Takayuki Ikezoe, Kazuei Ogawa, Yuko Hashimoto, Kayo Harada-Shirado, Hiroshi Ohkawara, Norio Komatsu, Kotaro Shide, Kazuya Shimoda, Shuhei Koide, Motohiko Oshima, Atsushi Iwama, and Yasuchika Takeishi
  • Organizer: 2016 (58th) American Society of Hematology (ASH) Annual meeting and Exposition
  • Place of Presentation: San Diego
  • Year and Date: 2016-12-02
  • Int'l Joint Research
• [Presentation] The role of oncogene HMGA2 in the pathogenesis of myeloproliferative neoplasms (MPN) (2016)
  • Author(s): Koki Ueda, Kazuhiko Ikeda, Kazuei Ogawa, Yuko Hashimoto, Soji Morishita, Norio Komatsu, Kotaro Shide, Kazuya Shimoda, Atsushi Iwama, Yasuchika Takeishi
  • Organizer: The 78th Annual Meeting of the Japanese Society of Hematology
  • Place of Presentation: 横浜
  • Year and Date: 2016-10-13
• [Presentation] The role of HMGA2 in the pathogenesis of myeloproliferative neoplasms (MPNs) (2016)
  • Author(s): Koki Ueda, Kazuhiko Ikeda, Kazuei Ogawa, Yuko Hashimoto, Soji Morishita, Norio Komatsu, Kotaro Shide, Kazuya Shimoda, Atsushi Iwama, Yasuchika Takeishi
  • Organizer: The 5th JCA-AACR Special Joint Conference
  • Place of Presentation: 舞浜
  • Year and Date: 2016-07-13
  • Int'l Joint Research
• [Remarks] 福島県立医科大学 血液内科学講座 研究業績
  • URL: http://www.fmu.ac.jp/home/hemato/kenkyu.html