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

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08759
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Nagoya 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
• 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

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.

Free Research Field

血液内科学

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。