ストレス応答に関与するヒストンメチル化の異常が造血幹細胞に与える影響

2015 Fiscal Year Annual Research Report

• Project/Area Number: 26860729
• Research Institution: Shiga University of Medical Science
• Principal Investigator: 河原 真大 滋賀医科大学, 医学部, 助教 (80617449)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 白血病 / ヒストンメチル化 / 造血幹細胞

Outline of Annual Research Achievements

本研究は、ヒストン脱メチル化酵素KDM4Bの発現上昇が、DNA損傷応答を始めとするストレス応答にどのような影響を与えるのか、ならびに造血機能にどのような影響を及ぼすのか、について検討した。様々な白血病細胞株でKDM4Bをノックダウンして、DNA損傷を与える核種抗がん剤に対する抵抗性を解析したが、特に大きな変化を認めなかった。KDM4Bをレンチウイルスで造血幹細胞に強発現させて移植したところ、ドナー由来の造血細胞の動員を認めなかった。Cre-loxPシステムで発現誘導可能なトランスジェニックマウスを作成し、MX1-Creマウスと掛け合わせた後、pIpCでKDM4Bを誘導すると、顆粒球への分化異常が認められた。以上のことから、KDM4Bは顆粒球の分化誘導に関わっていることが示唆された。

Research Products

• [Journal Article] A Japanese family with X-linked sideroblastic anemia affecting females and manifesting as macrocytic anemia. (2016)
  • Author(s): 1)Katsurada T, Kawabata H, Kawabata D, Kawahara M, Nakabo Y, Takaori-Kondo A, Yoshida Y.
  • Journal Title: Int J Hematol. Volume: E-pub Pages: E-pub Feb 10
  • Peer Reviewed
• [Journal Article] Hypomethylation of the Treg-Specific Demethylated Region in FOXP3 Is a Hallmark of the Regulatory T-cell Subtype in Adult T-cell Leukemia. (2016)
  • Author(s): Shimazu Y, Shimazu Y, Hishizawa M, Hamaguchi M, Nagai Y, Sugino N, Fujii S, Kawahara M, Kadowaki N, Nishikawa H, Sakaguchi S, Takaori-Kondo A.
  • Journal Title: Cancer Immunol Res. Volume: 4 Pages: 136-45
  • DOI: 10.1158/2326-6066.CIR-15-0148.
  • Peer Reviewed
• [Journal Article] T memory stem cells are the hierarchical apex of adult T-cell leukemia. (2015)
  • Author(s): Yuya Nagai†, Masahiro Kawahara†, Masakatsu Hishizawa, Yayoi Shimazu, Noriko Sugino, Sumie Fujii, Norimitsu Kadowaki and Akifumi Takaori-Kondo. († These authors equally contributed to this work.)
  • Journal Title: Blood Volume: 125 Pages: 3527-3535
  • DOI: 10.1182/blood-2014-10-607465.
  • Peer Reviewed
• [Presentation] Genetic and cytologic analyses about early T cell precursor acute lymphoblastic leukemia (2015)
  • Author(s): Ryusuke Yamamoto, Masahiro Kawahara, Yuya Nagai, Katsuyuki Ohmori, Yayoi Shimazu, Noriko Sugino, Sumie Fujii, Goichi Tatsumi and Akifumi Takaori-Kondo
  • Organizer: 日本血液学会
  • Place of Presentation: 金沢
  • Year and Date: 2015-10-16 – 2015-10-18
• [Presentation] Generation of engraftable leukemic stem cells from iPS cells derived from a secondary AML patient (2015)
  • Author(s): Kazuhisa Chonabayashi, Masahiro Kawahara, Masatoshi Nishizawa, Akifumi Takaori-Kondo, Shinya Yamanaka, and Yoshinori Yoshida
  • Organizer: 日本血液学会
  • Place of Presentation: 金沢
  • Year and Date: 2015-10-16 – 2015-10-18
• [Presentation] LSD1 regulates myeloid differentiation via affecting the enhancer activity of GFI1 (2015)
  • Author(s): Noriko Sugino, Masahiro Kawahara, Akinori Kanai, Hirotaka Matsui, Goichi Tatsumi, Ryusuke Yamamoto, Yuya Nagai, Sumie Fujii, Yayoi Shimazu, Masakatsu Hishizawa, Toshiya Inaba, Takayoshi Suzuki, and Akifumi Takaori-Kondo
  • Organizer: 日本血液学会
  • Place of Presentation: 金沢
  • Year and Date: 2015-10-16 – 2015-10-18
• [Presentation] The hierarchy in adult T-cell leukemia that originates from T memory stem cells (2015)
  • Author(s): Yuya Nagai, Masahiro Kawahara, Masakatsu Hishizawa, Yayoi Shimazu, Noriko Sugino, Sumie Fujii, Ryusuke Yamamoto, Goichi Tatsumi, Norimitsu Kadowaki, Akifumi Takaori-Kondo
  • Organizer: 日本血液学会
  • Place of Presentation: 金沢
  • Year and Date: 2015-10-16 – 2015-10-18
• [Presentation] Hypomethylation of the TSDR is a hallmark of the Treg subtype in adult T-cell leukemia (2015)
  • Author(s): Yayoi Shimazu, Yutaka Shimazu, Masakatsu Hishizawa, Masahide Hamaguchi, Yuya Nagai, Noriko Sugino, Sumie Fujii, Masahiro Kawahara, Norimitsu Kadowaki, Hiroyoshi Nishikawa, Shimon Sakaguchi, Akifumi Takaori-Kondo
  • Organizer: 日本血液学会
  • Place of Presentation: 金沢
  • Year and Date: 2015-10-16 – 2015-10-18