文章：

转录组分析揭示，即使具有相似的遗传背景，原发性浆细胞白血病与多发性骨髓瘤之间仍存在显著差异

Transcriptome analysis reveals significant differences between primary plasma cell leukemia and multiple myeloma even when sharing a similar genetic background

原文发布日期：2019-11-20

DOI: 10.1038/s41408-019-0253-1

类型: Article

开放获取: 是

英文摘要：

Primary plasma cell leukemia (pPCL) is a highly aggressive plasma cell dyscrasia characterised by short remissions and very poor survival. Although the 17p deletion is associated with poor outcome and extramedullary disease in MM, its presence does not confer the degree of aggressiveness observed in pPCL. The comprehensive exploration of isoform expression and RNA splicing events may provide novel information about biological differences between the two diseases. Transcriptomic studies were carried out in nine newly diagnosed pPCL and ten MM samples, all of which harbored the 17p deletion. Unsupervised cluster analysis clearly distinguished pPCL from MM samples. In total 3584 genes and 20033 isoforms were found to be deregulated between pPCL and MM. There were 2727 significantly deregulated isoforms of non-differentially expressed genes. Strangely enough, significant differences were observed in the expression of spliceosomal machinery components between pPCL and MM, in respect of the gene, isoform and the alternative splicing events expression. In summary, transcriptome analysis revealed significant differences in the relative abundance of isoforms between pPCL and MM, even when they both had the 17p deletion. The mRNA processing pathway including RNA splicing machinery emerged as one of the most remarkable mechanisms underlying the biological differences between the two entities.
 

摘要翻译： 

原发性浆细胞白血病（pPCL）是一种高度侵袭性的浆细胞恶液质，其特征是缓解期短且生存率极低。虽然17号染色体短臂缺失（17p缺失）与多发性骨髓瘤（MM）的不良预后和髓外病变相关，但其存在并不能解释pPCL中观察到的侵袭程度。对亚型表达和RNA剪接事件的全面探索可能为两种疾病之间的生物学差异提供新信息。研究人员对9例新诊断的pPCL和10例MM样本进行了转录组学研究，所有样本均携带17p缺失。无监督聚类分析清晰区分了pPCL与MM样本。总共发现3584个基因和20033种亚型在pPCL与MM之间存在失调现象。其中存在2727个非差异表达基因的显著失调亚型。值得注意的是，在剪接体机制组件的基因、亚型及可变剪接事件表达方面，pPCL与MM之间呈现显著差异。总之，转录组分析揭示即使同样携带17p缺失，pPCL与MM在亚型相对丰度方面仍存在显著差异。包含RNA剪接机制在内的mRNA加工通路，成为两者生物学差异中最显著的潜在机制之一。

原文链接：

Transcriptome analysis reveals significant differences between primary plasma cell leukemia and multiple myeloma even when sharing a similar genetic background