文章：

原发性浆细胞白血病的基因组分析揭示复杂的结构改变和高风险突变模式

Genomic analysis of primary plasma cell leukemia reveals complex structural alterations and high-risk mutational patterns

原文发布日期：2020-06-19

DOI: 10.1038/s41408-020-0336-z

类型: Article

开放获取: 是

英文摘要：

Primary plasma cell leukemia (pPCL) is a rare and aggressive form of multiple myeloma (MM) that is characterized by the presence of ≥20% circulating plasma cells. Overall survival remains poor despite advances of anti-MM therapy. The disease biology as well as molecular mechanisms that distinguish pPCL from non-pPCL MM remain poorly understood and, given the rarity of the disease, are challenging to study. In an attempt to identify key biological mechanisms that result in the aggressive pPCL phenotype, we performed whole-exome sequencing and gene expression analysis in 23 and 41 patients with newly diagnosed pPCL, respectively. The results reveal an enrichment of complex structural changes and high-risk mutational patterns in pPCL that explain, at least in part, the aggressive nature of the disease. In particular, pPCL patients with traditional low-risk features such as translocation t(11;14) or hyperdiploidy accumulated adverse risk genetic events that could account for the poor outcome in this group. Furthermore, gene expression profiling showed upregulation of adverse risk modifiers in pPCL compared to non-pPCL MM, while adhesion molecules and extracellular matrix proteins became increasingly downregulated. In conclusion, this is one of the largest studies to dissect pPCL on a genomic and molecular level.
 

摘要翻译： 

原发性浆细胞白血病（pPCL）是一种罕见且侵袭性强的多发性骨髓瘤（MM），其特征为外周血循环浆细胞比例≥20%。尽管抗MM治疗手段不断进步，患者总体生存率仍然较低。目前对pPCL与非pPCL型MM的疾病生物学特性及分子机制差异认识有限，且因该疾病罕见性导致研究难度极大。为探究导致侵袭性pPCL表型的关键生物学机制，我们分别对23例和41例新确诊pPCL患者进行了全外显子组测序和基因表达分析。研究结果揭示了pPCL中复杂结构改变和高风险突变模式的富集现象，这至少部分解释了该疾病的侵袭性本质。特别值得注意的是，具有传统低风险特征（如t(11;14)易位或超二倍体）的pPCL患者会累积不良风险遗传事件，这可能是该群体预后较差的原因。此外，基因表达谱分析显示，与非pPCL型MM相比，pPCL中不良风险修饰因子表达上调，而黏附分子和细胞外基质蛋白表达则显著下调。本研究是在基因组和分子水平解析pPCL的最大规模研究之一。

原文链接：

Genomic analysis of primary plasma cell leukemia reveals complex structural alterations and high-risk mutational patterns