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Comparative genomic analysis of high frequent ATL development due to HTLV-1 superinfection in Peru

Research Project

Project/Area Number 17H04600
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section海外学術
Research Field Medical genome science
Research InstitutionUniversity of Miyazaki

Principal Investigator

Morishita Kazuhiro  宮崎大学, 医学部, 教授 (80260321)

Co-Investigator(Kenkyū-buntansha) 鈴木 穣  東京大学, 大学院新領域創成科学研究科, 教授 (40323646)
中畑 新吾  宮崎大学, 医学部, 准教授 (80437938)
市川 朝永  宮崎大学, 医学部, 助教 (80586230)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2017: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
KeywordsATLL / HTLV-1 / ペルー / 糞線虫症 / 腸内細菌 / ATL / 糞線虫 / ゲノム解析 / 日和見感染 / 重複感染症 / 感染
Outline of Final Research Achievements

In Peru, Strongyloides stercoralis infection of human T-cell leukemia virus type 1 (HTLV-1) carriers causes adult T-cell leukemia (ATL) early and frequently. To elucidate the mechanism of ATL development in Peru, we performed a genome analysis of host and parasitic factors. In the S. stercoralis-coinfected carriers, the proportion of CADM1-positive ATL-like cells increased significantly, resulting in clonal proliferation of infected cells. Accelerated accumulation of driver mutations was observed in cases of ATL developed from S. stercoralis-coinfected carriers. Therefore, it is speculated that S. stercoralis coinfection may promote the accumulation of genomic mutations by abnormality of infectious immune defense mechanisms including gut microbiota.

Academic Significance and Societal Importance of the Research Achievements

HTLV-1感染者は世界で2000万人以上と言われており、日本以外の地域では、糞線虫症がATL発症の最大の危険因子と考えられる。本研究で得られた糞線虫重複感染により促進されるATL発症機構は、ペルーのみならず、アフリカなどの開発途上国におけるATL発症予防、治療に還元できる重要な基礎データとなりうる。さらに、宿主(感染リンパ球、腸内細菌叢)及び病原体(HTLV-1)の包括的なゲノム情報及びバイオマテリアルは、HTLV-1感染から長期の潜伏期に起こる宿主―病原体の相互作用に基づいた感染細胞のがん化メカニズムの理解において重要な情報を与えるものと思われる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (26 results)

All 2020 2019 2018 Other

All Int'l Joint Research (3 results) Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (19 results) (of which Int'l Joint Research: 4 results,  Invited: 4 results)

  • [Int'l Joint Research] Institute of Tropical Med.and Inf Dis./Peruvian University Cayetano Heredia(ペルー)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Peruvian University Cayetano Heredia/Inst of Tropical Med and Infect Dis(ペルー)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] Cayetano Heredia University(ペルー)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Clinical significance of soluble CADM1 as a novel marker for adult T-cell leukemia/lymphoma.2020

    • Author(s)
      Nakahata S, Syahrul C, Nakatake A, Sakamoto K, Yoshihama M, Nishikata I, Ukai Y, Matsuura T, Kameda T, Shide K, Kubuki Y, Hidaka T, Kitanaka A, Ito A, Takemoto S, Nakano N, Saito M, Iwanaga M, Sagara Y, Mochida K, Amano M, Maeda K, Sueoka E, Okayama A, Utsunomiya A, Shimoda K, Watanabe T, Morishita K.
    • Journal Title

      Haematologica

      Volume: 105 Issue: 2 Pages: 1-1

    • DOI

      10.3324/haematol.2019.234096

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Novel PRMT5-mediated arginine methylations of HSP90A are essential for maintenance of HSP90A function in NDRG2low ATL and various cancer cells.2020

    • Author(s)
      Ichikawa T, Shanab O, Nakahata S, Shimosaki S, Manachai N, Ono M, Iha H, Shimoda K, Morishita K
    • Journal Title

      Biochim Biophys Acta Mol Cell Res

      Volume: 1867 Issue: 2 Pages: 118615-118615

    • DOI

      10.1016/j.bbamcr.2019.118615

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The regulation of NDRG2 expression during ATLL development after HTLV-1 infection.2019

    • Author(s)
      Ichikawa T, Nakahata S, Fujii M, Iha H, Shimoda K, Morishita K.
    • Journal Title

      Biochim Biophys Acta Mol Basis Dis

      Volume: 1865 Issue: 10 Pages: 2633-2646

    • DOI

      10.1016/j.bbadis.2019.07.001

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Degradation of p47 by autophagy contributes to CADM1 overexpression in ATLL cells through the activation of NF-κB.2019

    • Author(s)
      Sarkar B, Nishikata I, Nakahata S, Ichikawa T, Shiraga T, Saha HR, Fujii M, Tanaka Y, Shimoda K, Morishita K.
    • Journal Title

      Sci Rep

      Volume: 9 Issue: 1 Pages: 3491-3491

    • DOI

      10.1038/s41598-019-39424-7

    • NAID

      120006825908

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 1.Toward the practical application of novel diagnostic tests and development of early detection markers for Adult T-Cell Leaukemia/Lymphoma in HTLV-1-carriers by host-parasite interaction in Peru.2019

    • Author(s)
      Shingo Nakahata, Eiji Nagayasu, Kazuhiro Morishita, Hruhiko Maruyama, Yutaka Suzuki, Masao Iwanaga, Yuetsu Tanaka, Martin Montes, Eduardo Gotuzzo.
    • Organizer
      19th International Conference On Human Retrovirology
    • Related Report
      2019 Annual Research Report
  • [Presentation] 2.ペルーにおける糞線虫重複感染によるATLL発症機構解明とその発症予防・治療法の開発を目指して2019

    • Author(s)
      森下和広、中畑新吾、長安英治、丸山治彦、鈴木穣、岩永正子、田中勇悦、Martin Montes、Eduardo Gotuzzo
    • Organizer
      第6回日本HTLV-1学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] EZH2 overexpression in ATL promotes epigenetic silencing of tumor suppressor gene NDRG2.2019

    • Author(s)
      Tomonaga Ichikawa, Shingo Nakahata, and Kazuhiro Morishita.
    • Organizer
      第6回日本HTLV-1学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Toward the practical application of novel diagnostic tests and development of early detection markers for Adult T-Cell Leaukemia/Lymphoma in HTLV-1-carriers by host-parasite interaction in peru2019

    • Author(s)
      Shingo Nakahata, Eiji Nagayasu, Kazuhiro Morishita, Hruhiko Maruyama, Yutaka Suzuki, Masao Iwanaga, Yuetsu Tanaka, Martin Montes, Eduardo Gotuzzo
    • Organizer
      19th INTERNATIONAL CONFERENCE ON HUMAN RETROVIROLOGY
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cell adhesion molecule 1 (CADM1) is an attractive target for the diagnosis and treatment of adult T-cell leukemia/lymphoma.2019

    • Author(s)
      Tomonaga Ichikawa, Ayako Nakatake, Bidhan Sarker, Shingo Nakahata, Kuniyo Sakamoto, Shunsuke Shimosaki, Ichiro Nishikata, Toshiyuki Shiraga, Kazuhiro Morishita
    • Organizer
      19th INTERNATIONAL CONFERENCE ON HUMAN RETROVIROLOGY
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ATLにおけるCADM1発現の機能とその臨床的意義2019

    • Author(s)
      中畑新吾、Chilmi Syahrul、Yanuar Fauzi、市川朝永、森下和広
    • Organizer
      第6回日本HTLV-1学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ATLLにおける可溶性CADM1の産生機序2019

    • Author(s)
      吉浜麻生、中畑新吾、市川朝永、森下和広
    • Organizer
      第6回日本HTLV-1学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Development of a therapeutic antibody targeting CADM1 for the treatment of ATLL2019

    • Author(s)
      Syahrul Chilmi、中畑新吾、市川朝永、松浦正、黒澤仁、森下和広
    • Organizer
      第81回日本血液学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 成人T細胞白血病/リンパ腫(ATLL)の発症機構2018

    • Author(s)
      森下和広
    • Organizer
      日本人類遺伝学会主催 第25回臨床採苗遺伝学セミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] HTLV-1 infection in Peru and Japan2018

    • Author(s)
      Kazuhiro Morishita
    • Organizer
      第18回日秘国際医学シンポジウム
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] EZH2 overexpression in ATL promotes epigenetic silencing of tumor suppressor gene NDRG2.2018

    • Author(s)
      Tomonaga Ichikawa, Shingo Nakahata, and Kazuhiro Morishita.
    • Organizer
      The 9th JSH International Symposium
    • Related Report
      2018 Annual Research Report
  • [Presentation] Identification of novel antisense RNAs in the genome of bovine leukemia virus (BLV).2018

    • Author(s)
      Shingo Nakahata, Chikako Tani, Tomonaga Ichikawa, Hirohisa Mekata, Kazuhiro Morishita.
    • Organizer
      第30回世界牛病学会2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] トランスフェリン受容体抗体はモガムリズマブ治療難治性のATLLの増殖抑制に有効である.2018

    • Author(s)
      中畑新吾、下崎俊介、市川朝永、亀田拓郎、日高智徳、久冨木庸子、黒澤仁、下田和哉、森下和広.
    • Organizer
      第5回日本HTLV-1学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] アルギニンメチル化転移酵素PRMT5異常活性によるATL発症機構の解析.2018

    • Author(s)
      市川朝永、Obeid Shanab、中畑新吾、尾野雅哉、伊波英克、中武彩子、阪本訓代、森下和広
    • Organizer
      第5回日本HTLV-1学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Short-form of BCL11B contributes to tumorigenesis of adult T-cell leukemia/lymphoma.2018

    • Author(s)
      Happy Kurnia Permatasari, Shingo Nakahata, Tomonaga Ichikawa, Kotaro Shide, Takuro Kameda, Kazuya Shimoda, Masaya Ono, Kazuhiro Morishita.
    • Organizer
      第5回日本HTLV-1学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ATLにおけるオートファジーによるNF-κB負の制御因子p47の不活化は、NF-κBシグナルを増強しCADM1高発現をもたらす.2018

    • Author(s)
      中畑新吾、Bidhan Sarkar、西片一郎、市川朝永、藤井雅寛、井上純一郎、伊波英克、下田和哉、森下和広.
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Arginine methylation of HSP90A by protein arginine methyltransferase PRMT5 promotes development of adult T-cell leukemia.2018

    • Author(s)
      Tomonaga Ichikawa, Obeid Shanab, Shingo Nakahata, Masaya Ono, Hidekatsu Iha, and Kazuhiro Morishita
    • Organizer
      第77回日本癌学会.
    • Related Report
      2018 Annual Research Report
  • [Presentation] High efficacy of anti-TFR1 antibody against the growth of mogamulizmab-resistant ATLL cells.2018

    • Author(s)
      Shingo Nakahata, Shunsuke Shimosaki, Tomonaga Ichikawa, Takuro Kameda, Tomonori Hidaka, Yoko Kubuki, Gene Kurosawa, Kazuya Shimoda, Kazuhiro Morishita.
    • Organizer
      第80回日本血液学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Overexpression of EZH2 confers ATL development through the suppression of tumor suppressor gene NDRG2.2018

    • Author(s)
      Tomonaga Ichikawa, Shingo Nakahata, Kazuhiro Morishita.
    • Organizer
      第80回日本血液学会.
    • Related Report
      2018 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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