Identification of blood biomarkers predicting clinical efficacy of molecular targeting agents in multiple myeloma

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K09855
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• 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): 桶本 和男 名古屋市立大学, 大学院薬学研究科, 助教 (50415486) ; 前川 京子 同志社女子大学, 薬学部, 教授 (70270626)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 多発性骨髄腫 / 分子標的薬 / バイオマーカー / マイクロRNA / セルフリーDNA / 脂質 / 血液 / 病態進展

Outline of Final Research Achievements

The purpose of this study is to explore predictive or prognostic biomarkers in blood in patients with multiple myeloma (MM). Cell free nuclear acids such as microRNA and cfDNA isolated from peripheral blood were analyzed by next generation sequencing in association with clinical information including patients’ prognosis and sensitivity to molecular targeting agents. Our study identified several serum microRNAs associated with sensitivity to bortezomib therapy. Sequential genetic analysis of cfDNAs in the same patients could identify some specific mutations relevant to the disease progression in MM. As well, serum lipid metabolites were comprehensively analyzed. It identified some lipid metabolites which might predict poor response to bortezomib plus dexamethasone therapy and occurrence of grade 2 or higher bortezomib-induced peripheral neuropathy. Further studies are needed to validate such candidate biomarkers in prospective large-scale studies.

Free Research Field

血液内科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、採取が簡便で臨床応用しやすい血液サンプルから診断マーカーとして血清中の遊離核酸と脂質代謝物を検討した点が特色である。これまでの造血器腫瘍、特に多発性骨髄腫領域では、その測定系や評価法は十分に確立されていない。本研究により、リキッドバイオプシーの臨床応用に向けた新たな基盤を形成できたと考えている。