Novel molecular mechanism of maintenance of stemness through a DNA methylation regulator in normal and malignant hematopoiesis

• Project/Area Number: 15K09452
• 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, 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): 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: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 白血病

Outline of Final Research Achievements

Recently, emerging evidence has revealed the important role of epigenetic regulation of gene expression. In the present study, I analyzed molecular mechanism of maintenance of stemness in normal and malignant hematopoiesis through a DNA methylation regulator, in which little was still known about its function. Molecular and biological analysis of several new mouse models of leukemia using conditional ablation and inducible expression of the regulator highlighted an interesting characteristic closely associated with malignant hematopoiesis, which had not been elucidated yet. Currently, I am investigating this property extensively.

Research Products

• [Journal Article] Eya2, a target activated by Plzf, is critical for PLZF-RARA-induced leukemogenesis. (2017)
  • Author(s): Ono R, Masuya M, Ishii S, Katayama N, Nosaka T.
  • Journal Title: Mol Cell Biol Volume: 印刷中 Issue: 13
  • DOI: 10.1128/mcb.00585-16
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] MYD88, CD79B, and CARD11 gene mutations in CD5-positive diffuse large B-cell lymphoma. (2017)
  • Author(s): Takeuchi, T, Yamaguchi M, Kobayashi K, Miyazaki K, Tawara I, Imai H, Ono R, Nosaka T, Tanaka K, Katayama N.
  • Journal Title: Cancer Volume: 123 Issue: 7 Pages: 1166-1173
  • DOI: 10.1002/cncr.30404
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Expressions of SH3BP5, LMO3, and SNAP25 in diffuse large B-cell lymphoma cells and their association with clinical features. (2016)
  • Author(s): Kobayashi K, Yamaguchi M, Miyazaki K, Imai H, Yokoe K, Ono R, Nosaka T, Katayama N.
  • Journal Title: Cancer Med Volume: 5 Issue: 8 Pages: 1802-1809
  • DOI: 10.1002/cam4.753
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Novel working hypothesis for pathogenesis of hematological malignancies: combination of mutations-induced cellular phenotypes determines the disease (cMIP-DD). (2016)
  • Author(s): Kitamura T, Watanabe-Okochi N, Enomoto Y, Nakahara F, Oki T, Komeno Y, Kato N, Doki N, Uchida T, Kagiyama Y, Togami K, Kawabata KC, Nishimura K, Hayashi Y, Nagase R, Saika M, Fukushima T, Asada S, Fujino T, Izawa Y, Horikawa S, Fukuyama T, Tanaka Y, Ono R, Goyama S, Nosaka T, Kitaura J, Inoue D
  • Journal Title: Journal of Biochemistry Volume: 159 Issue: 1 Pages: 17-25
  • DOI: 10.1093/jb/mvv114
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Eya2 is critical for an aberrant self-renewal in PLZF-RARA-induced leukemogenesis. (2017)
  • Author(s): Ono R, Masuya M, Ishii S, Katayama N, Nosaka T.
  • Organizer: 第79回日本血液学会学術集会
• [Presentation] PLZF関連白血病発症における新規分子機構の解析 (2016)
  • Author(s): 小埜良一、桝屋正浩、石井聡美、片山直之、野阪哲哉
  • Organizer: 第78回日本血液学会学術集会
  • Place of Presentation: パシフィコ横浜(神奈川県・横浜市)
• [Presentation] MYD88, CD79B, and CD79A Gene Mutations in CD5-Positive Diffuse Large B-Cell Lymphoma (2016)
  • Author(s): Toshifumi Takeuchi, Motoko Yamaguchi, Kyoko Kobayashi, Kana Miyazaki, Hiroshi Imai, Ryoichi Ono, Isao Tawara, Tetsuya Nosaka, Kyosuke Tanaka and Naoyuki Katayama
  • Organizer: The 58th American Society of Hematology Annual Meeting and Exposition
  • Place of Presentation: San Diego (米国)
  • Int'l Joint Research
• [Presentation] びまん性大細胞型B細胞リンパ腫細胞におけるSH3BP5, LMO3, SNAP25発現と臨床病態との関連 (2015)
  • Author(s): 小林 恭子, 山口 素子, 宮崎 香奈, 今井 裕, 小埜 良一, 野阪 哲哉, 片山 直之
  • Organizer: 第74回日本癌学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2015-10-10
• [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] 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