TERT promoter gene mutations in PTCL-NOS

• Project/Area Number: 17K08751
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Kurume University
• Principal Investigator: Arakawa Fumiko 久留米大学, 医学部, 助教 (50212618)
• Co-Investigator(Kenkyū-buntansha): 大島 孝一 久留米大学, 医学部, 教授 (50203766) ; 瀬戸 加大 久留米大学, 医学部, 客員教授 (80154665)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: リンパ腫 / hTERT / hTERT promoter / PTCL-NOS / ATLL / ｈTERT / TERT promoter / HRM解析

Outline of Final Research Achievements

We investigated the effect of human telomerase reverse transcriptase (hTERT), which is closely related to telomerase activity, on the promoter mutation, protein expression frequency, and pathology in T-cell lymphoma.　 Gene analysis of the hTERT promoter was performed in peripheral T-cell lymphoma, nonspecific (PTCL-NOS), and angioimmunoblastic T-cell lymphoma (AITL), which are common in T-cell lymphoma.　 Only 2 cases of PTCL-NOS had a gene mutation, and 1 case (known mutation site) also expressed protein, but the remaining 1 case (new site) did not express protein.　 The mutation of hTERT promoter does not seem to be directly related to its expression.　 A statistical analysis of protein expression revealed that only hTERT-expressing PTCL-NOS had a significantly poor prognosis.

Academic Significance and Societal Importance of the Research Achievements

悪性リンパ腫はリンパ球（主にB 細胞、T細胞由来）が癌化したものである。末梢性T細胞リンパ腫, 非特定 (PTCL-NOS)、血管免疫芽球性 T 細胞リンパ腫 (AITL)は極めて多様性に富む疾患である。hTERTとの関連性は、ほとんど調べられていない。今回、PTCL-NOSで、hTERTタンパクを発現しているT細胞リンパ腫が予後不良であったことは、予後の層別化を行うことが可能となり、今後、そのようなPTCL-NOSに対して何らかの新しい治療法に繋がることが期待される。

Research Products

• [Journal Article] Genomic Landscape of Young ATLL Patients Identifies Frequent Targetable CD28 Fusions (2020)
  • Author(s): Noriaki Yoshida, Kay Shigemori, Nicholas Donaldson, Christopher Trevisani, Nicolas A Cordero, Kristen E Stevenson, Xia Bu, Fumiko Arakawa, Mai Takeuchi, Koichi Ohshima, Akinori Yoda, Samuel Y Ng , David M Weinstock
  • Journal Title: Blood Volume: 135 Issue: 17 Pages: 1467-1471
  • DOI: 10.1182/blood.2019001815
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Clinical Features, Pathological Features, and Treatment Outcomes of 22 Patients with Aggressive Adult T-cell Leukemia-lymphoma Treated with a Humanized CCR4 Antibody (Mogamulizumab) at a Single Institution during a 6-year Period (2012-2018) (2019)
  • Author(s): Kawano N, Yoshida N, Kawano S, Arakawa F, Miyoshi H, Yamada K, Nakashima K, Yoshida S, Kuriyama T, Tochigi T, Nakaike T, Shimokawa T, Yamashita K, Marutsuka K, Mashiba K, Kikuchi I, Ohshima K.
  • Journal Title: Internal Medicine Volume: 58 Issue: 15 Pages: 2159-2166
  • DOI: 10.2169/internalmedicine.2513-18
  • NAID: 130007686813
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2019-08-01
  • Peer Reviewed / Open Access