文章：

免疫球蛋白重链基因重排的分子谱分析揭示了多发性骨髓瘤患者新的潜在预后标志物

Molecular profiling of immunoglobulin heavy-chain gene rearrangements unveils new potential prognostic markers for multiple myeloma patients

原文发布日期：2020-02-06

DOI: 10.1038/s41408-020-0283-8

类型: Article

开放获取: 是

英文摘要：

Multiple myeloma is a heterogeneous disease whose pathogenesis has not been completely elucidated. Although B-cell receptors play a crucial role in myeloma pathogenesis, the impact of clonal immunoglobulin heavy-chain features in the outcome has not been extensively explored. Here we present the characterization of complete heavy-chain gene rearrangements in 413 myeloma patients treated in Spanish trials, including 113 patients characterized by next-generation sequencing. Compared to the normal B-cell repertoire, gene selection was biased in myeloma, with significant overrepresentation of IGHV3, IGHD2 and IGHD3, as well as IGHJ4 gene groups. Hypermutation was high in our patients (median: 8.8%). Interestingly, regarding patients who are not candidates for transplantation, a high hypermutation rate (≥7%) and the use of IGHD2 and IGHD3 groups were associated with improved prognostic features and longer survival rates in the univariate analyses. Multivariate analysis revealed prolonged progression-free survival rates for patients using IGHD2/IGHD3 groups (HR: 0.552, 95% CI: 0.361−0.845, p = 0.006), as well as prolonged overall survival rates for patients with hypermutation ≥7% (HR: 0.291, 95% CI: 0.137−0.618, p = 0.001). Our results provide new insights into the molecular characterization of multiple myeloma, highlighting the need to evaluate some of these clonal rearrangement characteristics as new potential prognostic markers.
 

摘要翻译： 

多发性骨髓瘤是一种异质性疾病，其发病机制尚未完全阐明。尽管B细胞受体在骨髓瘤发病机制中起关键作用，但克隆性免疫球蛋白重链特征对预后的影响尚未得到广泛探索。本研究对413例西班牙临床试验中接受治疗的骨髓瘤患者进行了完整重链基因重排特征分析，其中包含113例通过二代测技术进行特征分析的患者。与正常B细胞库相比，骨髓瘤的基因选择存在偏好性，IGHV3、IGHD2、IGHD3及IGHJ4基因组的表达显著过高。患者群体的高突变率较高（中位数：8.8%）。值得注意的是，在不适合移植的患者中，单因素分析显示高突变率（≥7%）及使用IGHD2和IGHD3基因组与改善的预后特征和更长的生存期相关。多因素分析显示，使用IGHD2/IGHD3基因组的患者无进展生存期延长（风险比：0.552，95%置信区间：0.361-0.845，p=0.006），而高突变率≥7%的患者总生存期延长（风险比：0.291，95%置信区间：0.137-0.618，p=0.001）。我们的研究结果为多发性骨髓瘤的分子特征提供了新见解，强调需要评估部分克隆重排特征作为新的潜在预后标志物。

原文链接：

Molecular profiling of immunoglobulin heavy-chain gene rearrangements unveils new potential prognostic markers for multiple myeloma patients