文章：

多发性骨髓瘤髓外病变中临床结局与分子特征的整合

Integration of clinical outcomes and molecular features in extramedullary disease in multiple myeloma

原文发布日期：2024-12-23

DOI: 10.1038/s41408-024-01190-9

类型: Article

开放获取: 是

英文摘要：

Multiple myeloma (MM) remains incurable despite novel therapeutics. A major contributor to the development of relapsed/refractory and resistant MM is extraosseous extramedullary disease (EMD), whose molecular biology is still not fully understood. We analyzed 528 MM patients who presented to our institution between 2014 and 2021 and who had undergone molecular testing. We defined EMD as organ plasmacytoma distinct from bones and evaluated patients for the development of EMD with the goal of defining their molecular characteristics. Here, we show that RAS/BRAF mutations are likely essential for the development of EMD. Our results also indicate that the underlying reason for the negative outcomes in patients with poor prognostic factors such as duplication 1q and deletion 17p is largely due to the development of EMD. However, the presence of TP53 mutation remains a poor prognostic factor regardless of EMD development. Furthermore, mutation sites of TP53 were different between EMD versus non-EMD patients, with gain-of-function mutations enriched in patients with EMD. Our data highlights distinct molecular abnormalities in patients with EMD and provides potential mechanistic insights for novel therapeutic targets for the future.
 

摘要翻译： 

尽管新型疗法不断涌现，多发性骨髓瘤（MM）仍无法治愈。骨外髓外病变（EMD）是导致复发/难治性及耐药性MM发生的主要因素，其分子生物学机制尚未完全阐明。我们分析了2014年至2021年间在我院就诊并接受分子检测的528例MM患者。我们将EMD定义为独立于骨骼的器官浆细胞瘤，并评估患者发生EMD的情况，旨在明确其分子特征。本研究显示，RAS/BRAF基因突变可能是EMD发生的关键因素。结果还表明，1q扩增和17p缺失等不良预后因素导致患者结局较差的主要原因与EMD的发生密切相关。然而，无论是否发生EMD，TP53突变的存在始终是不良预后因素。此外，EMD与非EMD患者的TP53突变位点存在差异，EMD患者中功能获得性突变更为富集。我们的研究揭示了EMD患者特异的分子异常，为未来开发新型治疗靶点提供了潜在的机制见解。

原文链接：

Integration of clinical outcomes and molecular features in extramedullary disease in multiple myeloma