文章：

功能性高危多发性骨髓瘤患者的基因组特征研究

Genomic characterization of functional high-risk multiple myeloma patients

原文发布日期：2022-01-31

DOI: 10.1038/s41408-021-00576-3

类型: Article

开放获取: 是

英文摘要：

Multiple myeloma (MM) patients with suboptimal response to induction therapy or early relapse, classified as the functional high-risk (FHR) patients, have been shown to have poor outcomes. We evaluated newly-diagnosed MM patients in the CoMMpass dataset and divided them into three groups: genomic high-risk (GHR) group for patients with t(4;14) or t(14;16) or complete loss of functional TP53 (bi-allelic deletion of TP53 or mono-allelic deletion of 17p13 (del17p13) and TP53 mutation) or 1q21 gain and International Staging System (ISS) stage 3; FHR group for patients who had no markers of GHR group but were refractory to induction therapy or had early relapse within 12 months; and standard-risk (SR) group for patients who did not fulfill any of the criteria for GHR or FHR. FHR patients had the worst survival. FHR patients are characterized by increased mutations affecting the IL-6/JAK/STAT3 pathway, and a gene expression profile associated with aberrant mitosis and DNA damage response. This is also corroborated by the association with the mutational signature associated with abnormal DNA damage response. We have also developed a machine learning based classifier that can identify most of these patients at diagnosis.
 

摘要翻译： 

对诱导治疗反应不佳或早期复发的多发性骨髓瘤（MM）患者，被归类为功能高危（FHR）患者，已被证明预后不良。我们评估了CoMMpass数据集中的新诊断MM患者，并将他们分为三组：基因组高危（GHR）组，包括具有t(4;14)或t(14;16)或功能性TP53完全丧失（TP53双等位基因缺失或17p13单等位基因缺失（del17p13）和TP53突变）或1q21增益和国际分期系统（ISS）3期的患者；FHR组，包括没有GHR组标志物但对诱导治疗难治或在12个月内早期复发的患者；以及标准风险（SR）组，包括不符合GHR或FHR任何标准的患者。FHR患者的生存期最差。FHR患者的特征包括影响IL-6/JAK/STAT3通路的突变增加，以及与异常有丝分裂和DNA损伤反应相关的基因表达谱。这与异常DNA损伤反应相关的突变特征相关联，也进一步证实了这一点。我们还开发了一种基于机器学习的分类器，可以在诊断时识别大多数这些患者。

原文链接：

Genomic characterization of functional high-risk multiple myeloma patients