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Exploration of the origin of classic Hodgkin lymphoma cells by clonal and genetic analyses

Research Project

Project/Area Number 21K16279
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionNational Hospital Organization Nagoya Medical Center

Principal Investigator

SUZUKI Yasuhiro  独立行政法人国立病院機構(名古屋医療センター臨床研究センター), その他部局等, 医師 (90898016)

Project Period (FY) 2021-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2021: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywordscomposite lymphoma / クローン解析 / PD-L1 / IgH::BCL2 / plasticity / Hodgkin/Reed-Sternberg細胞 / NGS / FISH / IgH-BCL2 / レーザーマイクロダイセクション
Outline of Research at the Start

ホジキンリンパ腫は腫瘍細胞であるHodgkin/Reed-Sternberg(HRS細胞)の割合が少ないこともあり、その遺伝子解析は他の造血器腫瘍に比べても遅れており、腫瘍の発症や進展のメカニズムはまだ十分には明らかにはされていない。我々は、クローンが同一であり共通のPD-L1変異をもつと考えられた同時期発症のcomposite lymphoma(ホジキンリンパ腫とNK/T細胞リンパ腫)を経験した。本研究は、この症例をホジキンリンパ腫発症モデルとして、両腫瘍のクローンの関連性を追跡することにより、HRS細胞の腫瘍の起源ならびに進展の分子遺伝学的メカニズムを明らかにすることを目的とする。

Outline of Final Research Achievements

In classic Hodgkin lymphoma (cHL), the mechanisms of tumor pathogenesis and progression are not fully elucidated. We experienced a case with composite lymphoma (cHL and NK/T cell lymphoma) with identical clones and common PD-L1 abnormality and another case with synchronous lymphoma (cHL and follicular lymphoma) with identical clones. In this study, we analyzed these cases in detail pathologically and molecular genetically, and evaluated the relationship among these tumors. By these analyses, we explored the molecular mechanisms about the tumor origin and progression of cHL cells.

Academic Significance and Societal Importance of the Research Achievements

ホジキンリンパ腫とのまれなcomposite/synchronous lymphoma症例を詳細に解析し、両腫瘍の関連性を追跡することにより、HRS細胞の腫瘍の起源ならびに進展の分子メカニズムの解析を行った。これらのまれなリンパ腫の詳細な解析により、腫瘍の可塑性(plasticity)や細胞系統をまたぐ転化(transdifferentation)に関する重要な知見を得ることができたことは学術的な意義があるものと考えられる。また、これらの知見はリンパ腫発症の病態解明のみならず、治療開発という点でも有用となる可能性が考えられた。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (6 results)

All 2023 2022 2021

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Frequent genetic alterations in immune checkpoint-related genes in intravascular large B-cell lymphoma2021

    • Author(s)
      Shimada Kazuyuki、Yoshida Kenichi、Suzuki Yasuhiro、Iriyama Chisako、Inoue Yoshikage、Sanada Masashi、Kataoka Keisuke、Yuge Masaaki、Takagi Yusuke、Kusumoto Shigeru、Masaki Yasufumi、Ito Takahiko、Inagaki Yuichiro、Okamoto Akinao、Kuwatsuka Yachiyo、Nakatochi Masahiro、Shimada Satoko、Miyoshi Hiroaki et al.
    • Journal Title

      Blood

      Volume: 137 Issue: 11 Pages: 1491-1502

    • DOI

      10.1182/blood.2020007245

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 同時期の別部位にホジキンリンパ腫と濾胞性リンパ腫を併発した一例2023

    • Author(s)
      鈴木康裕、中別府聖一郎、安田貴彦、佐藤啓、山田朋美、眞田昌、飯田浩充、大塚眞紀、永井宏和
    • Organizer
      第63回 日本リンパ網内系学会学術集会・総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Interim PET-guided ABVD or ABVD/escalated BEACOPP for newly diagnosed advanced-stage classic Hodgkin lymphoma (JCOG1305, INNOVATE-HL study)2023

    • Author(s)
      Shigeru Kusumoto, Wataru Munakata, Ryunosuke Machida, Takashi Terauchi, Hiroaki Onaya, Masahiko Oguchi, Shinsuke Iida, Kisato Nosaka, Yasuhiro Suzuki, Yasuhiko Harada, Kana Miyazaki, et al.
    • Organizer
      64th ASH Annual Meeting and Exposition
    • Related Report
      2022 Annual Research Report
  • [Presentation] Prospective Study on the Usefulness of Liquid Biopsy in Patients with Unknown Fever Suspected of Malignant Lymphoma2023

    • Author(s)
      Akinao Okamoto, Masashi Sanada, Takahiko Yasuda, Seiichi Kato, Akira Sato, Kosei Matsue, Hiroki Hosoi, Masahiro Yoshida, Satsuki Murakami, Eisei kondo, Yasufumi Masaki, Yasuhiro Suzuki, Kana Miyazaki, et al.
    • Organizer
      64th ASH Annual Meeting and Exposition
    • Related Report
      2022 Annual Research Report
  • [Presentation] PD-L1増幅と3’-UTR欠失の両異常を有し、ホジキンリンパ腫からPEL-like lymphomaへのクローン進展が疑われた一例2022

    • Author(s)
      鈴木康裕、安田貴彦、佐藤啓、坂田征士、竹内賢吾、市原周、西村理恵子、眞田昌、中村栄男、飯田浩充、永井宏和
    • Organizer
      第62回 日本リンパ網内系学会学術集会・総会
    • Related Report
      2021 Research-status Report
  • [Presentation] Clinical Outcomes of Elderly Patients with Advanced-Stage Classic Hodgkin Lymphoma Who Received an ABVD Regimen: A Multi-Center Retrospective Study in Japan (HORIZON study)2021

    • Author(s)
      Shinichi Makita, Shigeru Kusumoto, Akiko Miyagi Maeshima, Hiroya Hashimoto, Hideki Tsujimura, Toshiki Uchida, Hiroaki Inoue, Eiichi Ohtsuka, Mitsutoshi Kurosawa, Nobuyuki Takayama, Eiju Negoro, Yasuhiro Suzuki et al.
    • Organizer
      63rd ASH Annual Meeting and Exposition
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research

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Published: 2021-04-28   Modified: 2024-01-30  

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