文章：

基于蛋白质组学分型的慢性淋巴细胞白血病分类可为现代治疗提供预后判断并识别新的治疗靶点

Proteomic profiling based classification of CLL provides prognostication for modern therapy and identifies novel therapeutic targets

原文发布日期：2022-03-17

DOI: 10.1038/s41408-022-00623-7

类型: Article

开放获取: 是

英文摘要：

Protein expression for 384 total and post-translationally modified proteins was assessed in 871 CLL and MSBL patients and was integrated with clinical data to identify strategies for improving diagnostics and therapy, making this the largest CLL proteomics study to date. Proteomics identified six recurrent signatures that were highly prognostic of survival and time to first or second treatment at three levels: individual proteins, when grouped into 40 functionally related groups (PFGs), and systemically in signatures (SGs). A novel SG characterized by hairy cell leukemia like proteomics but poor therapy response was discovered. SG membership superseded other prognostic factors (Rai Staging, IGHV Status) and were prognostic for response to modern (BTK inhibition) and older CLL therapies. SGs and PFGs membership provided novel drug targets and defined optimal candidates for Watch and Wait vs. early intervention. Collectively proteomics demonstrates promise for improving classification, therapeutic strategy selection, and identifying novel therapeutic targets.
 

摘要翻译： 

在871例慢性淋巴细胞白血病（CLL）和单克隆B淋巴细胞增多症（MSBL）患者中，对384种总蛋白及翻译后修饰蛋白的表达进行了评估，并与临床数据整合，以确定改进诊断和治疗的策略，这使其成为迄今规模最大的CLL蛋白质组学研究。蛋白质组学分析识别出六个反复出现的特征群，这些特征群在三个层面均对患者生存期及首次或二次治疗时间具有高度预后价值：单个蛋白质水平、40个功能相关蛋白质组（PFGs）水平以及系统性特征群（SGs）水平。研究发现了一种新型SG，其蛋白质组学特征类似毛细胞白血病但对治疗反应不佳。SG的分类超越了其他预后因素（Rai分期、IGHV状态），并能预测对现代疗法（BTK抑制剂治疗）及传统CLL疗法的反应。SG和PFG的分类提供了新的药物靶点，并明确了适合观察等待与早期干预的最佳候选方案。总体而言，蛋白质组学在改善疾病分类、治疗策略选择及识别新治疗靶点方面展现出广阔前景。

原文链接：

Proteomic profiling based classification of CLL provides prognostication for modern therapy and identifies novel therapeutic targets