Analysis of lymphoma development through epigenetic dysregulation associated with reduced Tet2 function

• Project/Area Number: 26860717
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: University of Tsukuba
• Principal Investigator: Muto Hideharu 筑波大学, 医学医療系, 講師 (50709194)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: TET2 / T細胞性リンパ腫 / 濾胞性ヘルパーT細胞 / BCL6 / エピゲノム異常

Outline of Final Research Achievements

TET2 gene, which encodes an enzyme that converts methylcytosine to hydroxymethylcytosine, plays an important role for epigenetic regulation. TET2 gene mutation has been frequently found in a part of T-cell lymphomas as well as myeloid malignancies. We analyzed Tet2 knockdown mice and revealed that they developed T-cell lymphomas with follicular helper T-cell like features. Upregulation of Bcl6 expression through epigenetic dysregulation was associated with mechanism for lymphoma development. We guess that the similar mechanism exists in human T-cell lymphoma.

Research Products

• [Journal Article] TET2 as a gatekeeper for hematologic malignancies (2015)
  • Author(s): 武藤秀治, 坂田（柳元）麻実子, 千葉 滋
  • Journal Title: Rinsho Ketsueki Volume: 56 Issue: 6 Pages: 651-656
  • DOI: 10.11406/rinketsu.56.651
  • NAID: 130005093097
  • ISSN: 0485-1439, 1882-0824
  • Peer Reviewed
• [Journal Article] Reduced TET2 function leads to T-cell lymphoma with follicular helper T-cell-like features in mice. (2014)
  • Author(s): Muto H, Sakata-Yanagimoto M, Nagae G, Shiozawa Y, Miyake Y, Yoshida K, Enami T, Kamada Y, Kato T, Uchida K, Nanmoku T, Obara N, Suzukawa K, Sanada M, Nakamura N, Aburatani H, Ogawa S, Chiba S
  • Journal Title: Blood Cancer J. Volume: 12 Issue: 12 Pages: e264-e264
  • DOI: 10.1038/bcj.2014.83
  • Peer Reviewed / Open Access
• [Presentation] BCL6 locus is hypermethylated in human peripheral T-cell lymphomas (2015)
  • Author(s): 西澤翔子，坂田（柳元） 麻実子, 武藤 秀治, 榎並 輝和, 松原（中本） 理絵, Tran Nguyen, 野口 雅之, 中村 直哉, 千葉 滋
  • Organizer: 第77回日本血液学会学術総会
  • Place of Presentation: 石川県立音楽堂（金沢市）
  • Year and Date: 2015-10-17
• [Presentation] ヒト末梢性T細胞リンパ腫においてはBCL6領域が高メチル化されている (2015)
  • Author(s): 西澤翔子，坂田（柳元） 麻実子, 武藤 秀治, 榎並 輝和, 松原（中本） 理絵, 野口 雅之, 中村 直哉, 千葉 滋
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
  • Year and Date: 2015-10-10
• [Presentation] Genetic Analysis of T-cell Lymphoma Developed in TET2 Knockdown Mice (2014)
  • Author(s): Hideharu Muto, Mamiko Sakata-Yanagimoto, Yusuke Shiozawa, Terukazu Enami, Naoshi Obara, Seishi Ogawa, and Shigeru Chiba
  • Organizer: 第76回日本血液学会総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-11-02
• [Presentation] Genetic Analysis of T-cell Lymphoma Developed in TET2 Knockdown Mice (2014)
  • Author(s): Hideharu Muto, Mamiko Sakata-Yanagimoto, Yusuke Shiozawa, Terukazu Enami, Naoshi Obara, Seishi Ogawa, and Shigeru Chiba
  • Organizer: 第73回日本癌学会総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-26
• [Remarks] 筑波大学医学医療系血液内科
  • URL: http://www.ketsunai.com/
• [Remarks] 筑波大学医学医療系血液内科
  • URL: http://www.ketsunai.com/publication/