Elucidation of pathogenic mechanism of adult T-cell leukemia induced by abnormal ROS regulation

• Project/Area Number: 26461417
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Niigata University
• Principal Investigator: Takahashi Masahiko 新潟大学, 医歯学系, 准教授 (80377192)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ATL / HTLV-1 / USP10 / Tax / ストレス顆粒

Outline of Final Research Achievements

Adult T-cell leukemia (ATL) is an aggressive hematologic malignancy of poor prognosis caused by human T-cell leukemia virus type 1 (HTLV-1), and it is imperative to develop therapeutic drugs for chemotherapy against ATL. As arsenite or proteasome inhibitor bortezomib induce cell death in HTLV-1-infected T-cells, antitumor effect on ATL can be expected by using these drugs. In this study, we identified that ubiquitin-specific protease 10 (USP10) confers drug resistance phenotype to HTLV-1-infected T-cells. Based on this result, we are currently attempting to identify cellular defense mechanism against drug treatment that USP10 is involved.

Research Products

• [Journal Article] Human T-cell leukemia virus type 1 (HTLV-1) Tax1 oncoprotein but not HTLV-2 Tax2 induces the expression of OX40 ligand by interacting with p52/p100 and RelB. (2016)
  • Author(s): Motai Y, Takahashi M, Takachi T, Higuchi M, Hara T, Mizuguchi M, Aoyagi Y, Terai S, Tanaka Y, Fujii M.
  • Journal Title: Virus Genes. Volume: 52 Issue: 1 Pages: 4-13
  • DOI: 10.1007/s11262-015-1277-7
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] USP10 Is an Essential Deubiquitinase for Hematopoiesis and Inhibits Apoptosis of Long-Term Hematopoietic Stem Cells. (2016)
  • Author(s): Higuchi M, Kawamura H, Matsuki H, Hara T, Takahashi M, Saito S, Saito K, Jiang S, Naito M, Kiyonari H, Fujii M.
  • Journal Title: Stem Cell Reports Volume: ７ Issue: 6 Pages: 1116-1129
  • DOI: 10.1016/j.stemcr.2016.11.003
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Human T-cell leukemia virus type 1 Tax oncoprotein represses the expression of the BCL11B tumor suppressor in T-cells (2015)
  • Author(s): Takachi T, Takahashi M, Takahashi-Yoshita M, Higuchi M, Obata M, Mishima Y, Okuda S, Tanaka Y, Matsuoka M, Saitoh A, Green PL, Fujii M.
  • Journal Title: Cance Science Volume: 106(4) Issue: 4 Pages: 461-465
  • DOI: 10.1111/cas.12618
  • NAID: 120006844098
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] RASAL3, a novel hematopoietic RasGAP protein, regulates the number and functions of NKT cells. (2015)
  • Author(s): Saito S, Kawamura T, Higuchi M, Kobayashi T, Yoshita-Takahashi M, Yamazaki M, Abe M, Sakimura K, Kanda Y, Kawamura H, Jiang S, Naito M, Yoshizaki T, Takahashi M, Fujii M.
  • Journal Title: Eur J Immunol. Volume: in press Issue: 5 Pages: 1512-1523
  • DOI: 10.1002/eji.201444977
  • Peer Reviewed
• [Journal Article] Downregulation of proapoptotic Bim augments IL-2-independent T-cell transformation by human T-cell leukemia virus type-1 Tax. (2014)
  • Author(s): Higuchi M, Takahashi M, Tanaka Y, Fujii M.
  • Journal Title: Cancer Med. Volume: 3 Issue: 6 Pages: 1605-1614
  • DOI: 10.1002/cam4.329
  • Peer Reviewed / Open Access / Acknowledgement Compliant