Ig-Seq of multiple myeloma patients for liquid biopsy monitoring

A small cohort of t(4;14) multiple myeloma patients were enrolled in this study. We used immunoglobulin heavy and light chain amplicon sequencing to identify and monitor the myeloma clones during the disease course. We compared these data to other monitoring methods: ddPCR of patient-specific IgH-CDR3 sequences (identified in this NGS analysis), IGH-MMSET qPCR, multiparametric flow cytometry, M-protein and free light chain levels. Our aim was to assess the feasibility of liquid biopsy-based molecular methods with high sensitivity in the clinics of multiple myeloma.

本研究纳入了t(4;14)染色体易位型多发性骨髓瘤（multiple myeloma）患者小队列。我们采用免疫球蛋白重链与轻链扩增子测序（immunoglobulin heavy and light chain amplicon sequencing），对疾病进程中的骨髓瘤克隆进行识别与动态监测。我们将上述测序数据与其他监测手段进行了对照分析：包括本研究二代测序（next-generation sequencing, NGS）分析中鉴定的患者特异性免疫球蛋白重链互补决定区3（IgH-CDR3）序列的液滴数字PCR（ddPCR）、IGH-MMSET定量聚合酶链式反应（qPCR）、多参数流式细胞术（multiparametric flow cytometry），以及M蛋白（M-protein）与游离轻链（free light chain）水平检测。本研究旨在评估基于液体活检的高灵敏度分子检测方法在多发性骨髓瘤临床诊疗中的应用可行性。