Functional analysis of the Zinc finger E-box binding homeobox 1 (ZEB1/TCF8) gene in the multi-step leukemogenesis of adult T-cell leukemia/lymphoma

2010 Fiscal Year Final Research Report

• Project/Area Number: 19790344
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Virology
• Research Institution: University of Miyazaki
• Principal Investigator: NAKAHATA Shingo University of Miyazaki, 医学部, 助教 (80437938)
• Project Period (FY): 2007 – 2010
• Keywords: 白血病

Research Abstract

We identified that TCF8 at 10q11.2 is a candidate tumor-suppressor gene in acute-type adult-T cell leukemia/lymphoma (ATLL). The down-regulation of TCF8 expression by genetic and epigenetic abnormalities in ATLL was associated with resistance to TGF-beta1 treatment, which is one of well-known characteristics of ATL cells. The enforced expression of TCF8 partially restored the responsiveness of ATLL cells to TGF-beta1. Furthermore, TCF8 deficient mice frequently developed invasive CD4^+ T-cell lymphomas in thymus or in ascitic fluids. These findings suggest that TCF8 may become a new therapeutic target for ATLL.

Research Products

• [Journal Article] Downregulation of ZEB1 and overexpression of Smad7 contribute to resistance to GF-b-mediated growth suppression in adult T-cell leukemia/lympho ma. (2010)
  • Author(s): Nakahata S, Yamazaki S, Nakauchi H, Morishita K.
  • Journal Title: Oncogene. 29 Pages: 4157-4169
  • Peer Reviewed
• [Journal Article] Down-regulation TCF8 is involved in the leukemogenesis of adult T-cell leukemia/lympof ihoma. (2008)
  • Author(s): Hidaka T, Nakahata S, Hatakeyama K, Hamasaki M, Yamashita K, Kohno T, Arai Y, Taki T, Nishida K, Okayama A, Asada Y, Yamaguchi R, Tsubouchi H, Yokota J, Taniwaki M, Higashi Y, Morishita K.
  • Journal Title: Blood. 112 Pages: 383-393
  • Peer Reviewed
• [Presentation] 成人T細胞白血病細胞におけるCDKN1A遺伝子の転写はプロモーターのメチル化とZEB1 発現低下により抑制される (2010)
  • Author(s): 中畑新吾
  • Organizer: 第73回日本血液学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2010-09-25
• [Presentation] ATLLにおけるZEB1転写抑制はCCNG2及びCDKN1Aの転写抑制を介した細胞増殖をきたす (2009)
  • Author(s): 中畑新吾
  • Organizer: 第2回HTLV-1研究会・合同斑会議
  • Place of Presentation: 東京大学医科学研究所
  • Year and Date: 2009-08-30
• [Presentation] TCF8はSmad7を抑制しATLのTGF-beta1不能性を解除する (2008)
  • Author(s): 中畑新吾
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2008-10-12
• [Presentation] Downregulation of TCF8 is involved in ATLL development by the escape from TGF-beta1 during T cell differentiation. (2007)
  • Author(s): 中畑新吾
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: パシフィコ横
  • Year and Date: 2007-10-05
• [Book] Annual Review 血液(ATLの発症機構) (2010)
  • Author(s): 中畑新吾、森下和広
  • Total Pages: 132-138
  • Publisher: 中外医学社
• [Book] 血液フロンティ18巻(TCF8遺伝子発現抑制による成人T細胞白血病・リンパ腫発症機構) (2008)
  • Author(s): 中畑新吾、森下和広
  • Total Pages: 65-72
  • Publisher: 医薬ジャーナル社