Analysis of molecular mechanism in leukemogenesis through an epigenome regulator

• Project/Area Number: 24591390
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Mie University
• Principal Investigator: ONO RYOICHI 三重大学, 医学(系)研究科(研究院), 講師 (40422414)
• Co-Investigator(Renkei-kenkyūsha): NOSAKA Tetsuya 三重大学, 大学院医学系研究科, 教授 (30218309)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 白血病 / エピゲノム

Outline of Final Research Achievements

In this study, to focus on epigenetic alterations closely associated with leukemogenesis, I have generated conditional knockout mice of an epigenome regulator, analyzed malignant hematopoiesis of these mice combined with my leukemogenic mouse model, and characterized normal hematopoiesis of the mice. Conditional ablation of the target molecule induced no critical phenotypic changes in leukemogenesis, but led to interesting findings concerning self-renewal and differentiation of hematopoietic stem cells. I am further investigating the molecular mechanisms at the moment.

Research Products

• [Journal Article] Plzf drives MLL-fusion-mediated leukemogenesis specifically in long-term hematopoietic stem cells. (2013)
  • Author(s): Ono, R
  • Journal Title: Blood Volume: 122 Issue: 7 Pages: 1271-1283
  • DOI: 10.1182/blood-2012-09-456665
  • Peer Reviewed
• [Journal Article] Manipulation of human early T lymphopoiesis by coculture on human bone marrow stromal cells: Potential utility for adoptive immunotherapy (2013)
  • Author(s): Liu B, Ohishi K, Orito Y,N a k a mo r i Y, Nishikawa H, Ino K,Suzuki K, Matsumoto T,Masuya M,Hamada H, Mineno J, Ono R, Nosaka T, Shiku H, Katayama N.
  • Journal Title: Exp Hematol Volume: - Issue: 4 Pages: 367-376
  • DOI: 10.1016/j.exphem.2012.12.001
  • Peer Reviewed
• [Presentation] Expression of LMO3 and SNAP25 in Diffuse Large B-Cell Lymphoma Cells and Its Relation to Clinical Features (2014)
  • Author(s): Kobayashi K, Yamaguchi M, Miyazaki K, Imai H, Yokoe K, Ono R, Nosaka T, and Katayama N
  • Organizer: 第56回アメリカ血液学会
  • Place of Presentation: 米国カルフォルニア州サンフランシスコ
  • Year and Date: 2014-12-07
• [Presentation] 白血病発症におけるPlzfによる異常な自己複製をもたらす新規分子機構の解析 (2014)
  • Author(s): 小埜良一、桝屋正浩、片山直之、野阪哲哉
  • Organizer: 第76回日本血液学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-11-02
• [Presentation] An aberrant self-renewal program driven by Plzf is critical for leukemic transformation of hematopoietic stem cells by MLL fusion gene (2013)
  • Author(s): 小埜良一、野阪哲哉
  • Organizer: 第65回日本細胞生物学会大会
  • Place of Presentation: 名古屋
• [Presentation] MLL fusion genes transform hematopoietic stem cells through an aberrant self-renewal program by Plzf
  • Author(s): 小埜良一、桝屋正浩、中島秀明、榎本豊、宮田恵里、上迫努、伊藤守、鈴木圭、片山直之、北村俊雄、野阪哲哉
  • Organizer: 第74回日本血液学会学術集会
  • Place of Presentation: 京都
• [Remarks] 三重大学大学院医学系研究科 感染症制御医学・分子遺伝学
  • URL: http://www.medic.mie-u.ac.jp/microbiol/
• [Remarks] 三重大学大学院医学系研究科 感染症制御医学・分子遺伝学
  • URL: http://www.medic.mie-u.ac.jp/microbiol/index.html
• [Remarks] 小埜 良一 詳細
  • URL: http://www.crc.mie-u.ac.jp/seeds/contents/detail.php?mid=20121112-135914&t=r&url=