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Exploratory study to find predictive genomic biomarkers using liquid biopsy in multiple myeloma

Research Project

Project/Area Number 20K08759
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionNagoya City University

Principal Investigator

Iida Shinsuke  名古屋市立大学, 医薬学総合研究院(医学), 教授 (50295614)

Co-Investigator(Kenkyū-buntansha) 李 政樹  名古屋市立大学, 医薬学総合研究院(医学), 准教授 (00567539)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords多発性骨髄腫 / バイオマーカー / リキッドバイオプシー / cell free DNA / クローン進化 / 薬剤感受性 / cfDNA / ゲノムバイオマーカー
Outline of Research at the Start

多発性骨髄腫患者の予後は、新規薬剤の導入により改善し、生存期間中央値で5~6年に達している。しかし、予後は患者毎に多様である。日常診療で用いられる臨床病期や細胞遺伝学的検査のみでは、患者予後や薬剤感受性を予測することは困難である。骨髄腫細胞は体内で進化し多様なクローンが生まれていることから、骨髄のみならず髄外の腫瘍細胞も加味した包括的な分子病態解析が必要である。本研究により、骨髄および末梢血(単核球および血清cell free DNA: cfDNA)の分子病態を比較し、骨髄腫の病勢進行や薬剤感受性に関わる遺伝子変異を同定する。

Outline of Final Research Achievements

This study aimed to elucidate genetic mutations related to sensitivity or resistance to each drug and prognosis of the patients with multiple myeloma (MM). It was compared using clinical samples derived from marrow plasma cells and those of cell free DNA(cfDNA) in peripheral blood. As a result, various types of gene mutations and structural variants were identified in cfDNA relevant to clinical features but not in marrow plasma cells. It suggests that the genetic aberrations detected in cfDNA reflect those of other marrow sites from aspiration site in addition to the extramedullary lesions, and they determines the prognosis of the patients in MM especially with high-risk cytogenetic abnormalities. Further study is warranted to identify clinically available gene mutations in cfDNA related to the drug resistance and patient prognosis in MM.

Academic Significance and Societal Importance of the Research Achievements

本研究により、末梢血cfDNAにおいて、骨髄中の形質細胞の解析のみからは同定しえなかった遺伝子変異や構造異常を抽出できた。これは、多発性骨髄腫細胞は体内の骨髄や髄外病変など多くの部位でクローン進化しており、それが患者の病態を反映し生命予後や薬剤反応性に寄与すると考えられた。すなわち、多数例での末梢血cfDNA解析によって、薬剤耐性や予後に関連したバイオマーカーを同定すれば患者毎の至適な治療法を確立することが可能となる可能性が示された。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (5 results)

All 2021 2020

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (1 results)

  • [Journal Article] HLA genotyping in Japanese patients with multiple myeloma receiving bortezomib: An exploratory biomarker study of JCOG1105 (JCOG1105A1)2021

    • Author(s)
      Ri Masaki、Iida Shinsuke、Maruyama Dai、Sakabe Aya、Kamei Ryo、Nakashima Takuto、Tohkin Masahiro、Osaga Satoshi、Tobinai Kensei、Fukuhara Noriko、Miyazaki Kana、Tsukamoto Norifumi、Tsujimura Hideki、Yoshimitsu Makoto、Miyamoto Kenichi、Tsukasaki Kunihiro、Nagai Hirokazu
    • Journal Title

      Cancer Science

      Volume: 112 Issue: 12 Pages: 5011-5019

    • DOI

      10.1111/cas.15158

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genomic analysis of multiple myeloma using targeted capture sequencing in the Japanese cohort.2020

    • Author(s)
      Kanamori T, Sanada M, Ri M, Ueno H, Nishijima D, Yasuda T, Tachita T, Narita T, Kusumoto S, Inagaki A, Ishihara R, Murakami Y, Kobayashi N, Shiozawa Y, Yoshida K, Nakagawa MM, Nannya Y, Shiraishi Y, Chiba K, Tanaka H, Miyano S, Horibe K, Handa H, Ogawa S, Iida S.
    • Journal Title

      Br J Haematol.

      Volume: - Issue: 5 Pages: 755-763

    • DOI

      10.1111/bjh.16720

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Expression, mutation, and methylation of CRBN-pathway genes at pre- and post-lenalidomide treatment in multiple myeloma.2020

    • Author(s)
      Tachita T, Kinoshita S, Ri M, Aoki S, Asano A, Kanamori T, Yoshida T, Totani H, Ito A, Kusumoto S, Komatsu H, Yamagata K, Kubo K, Tohkin M, Fukuda S, Iida S.
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 4 Pages: 1333-1343

    • DOI

      10.1111/cas.14352

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical utility of target capture‐based panel sequencing in hematological malignancies: A multicenter feasibility study2020

    • Author(s)
      Yasuda T, Sanada M, Nishijima D, Kanamori T, Iijima Y, Hattori H, Saito A, Miyoshi H, Ishikawa Y, Asou N, Usuki K, Hirabayashi S, Kato M, Abe M.
    • Journal Title

      Cancer Science

      Volume: 111 Issue: 9 Pages: 3367-3378

    • DOI

      10.1111/cas.14552

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Cytogenetic risk/Genome-based medicine in multiple myeloma2021

    • Author(s)
      Takashi Kanamori, Shinsuke Iida
    • Organizer
      The 12th. JSH International Symposium 2021 in Kamakura
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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