Transcriptome analysis reveals molecular profiles associated with evolving steps of monoclonal gammopathies
Transcriptome analysis reveals molecular profiles associated with evolving steps of monoclonal gammopathies
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DOI：
10.3324/haematol.2013.087809
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发表时间：
2014-08-01
期刊：
影响因子：
10.1
通讯作者：
Gutierrez, Norma C.
中科院分区：
文献类型：
--
作者：
Lopez-Corral, Lucia;Antonio Corchete, Luis;Gutierrez, Norma C.
已经提出了一种多步模型，该模型描述疾病进展，从意义未定的单克隆丙种球蛋白病开始，持续到多发性骨髓瘤，有时会出现称为冒烟性骨髓瘤的中间实体，最后以髓外疾病结束。为了进一步了解转录组失调在正常浆细胞向克隆浆细胞以及惰性克隆浆细胞向恶性浆细胞转变中的作用，我们对 20 名意义未明的单克隆丙种球蛋白病患者、33 名高危冒烟性骨髓瘤患者和 41 名多发性骨髓瘤患者进行了基因表达谱分析。分析显示，与正常浆细胞相比，在意义未明的单克隆丙种球蛋白病、冒烟性骨髓瘤和多发性骨髓瘤中，有 126 个基因存在差异表达。有趣的是，126个显着差异表达基因中有17个和9个是小核仁RNA分子和锌指蛋白。与意义未明的单克隆丙种球蛋白病相比，在有症状和无症状的多发性骨髓瘤中，多种促凋亡基因（AKT1 和 AKT2）下调，抗凋亡基因（APAF1 和 BCL2L1）上调。当我们寻找那些在单克隆丙种球蛋白病的进化阶段逐渐调节的基因时，八个 snoRNA 显示出逐渐增加，而 APAF1、VCAN 和 MEGF9 显示出逐渐下调。总之，我们的数据表明，尽管意义未定的单克隆丙种球蛋白病、冒烟性骨髓瘤和多发性骨髓瘤根据其基因表达谱并不能明确区分，但一些信号通路和基因在转化过程的不同步骤中显着失调。
A multistep model has been proposed of disease progression starting in monoclonal gammopathy of undetermined significance continuing through multiple myeloma, sometimes with an intermediate entity called smoldering myeloma, and ending in extramedullary disease. To gain further insights into the role of the transcriptome deregulation in the transition from a normal plasma cell to a clonal plasma cell, and from an indolent clonal plasma cell to a malignant plasma cell, we performed gene expression profiling in 20 patients with monoclonal gammopathy of undetermined significance, 33 with high-risk smoldering myeloma and 41 with multiple myeloma. The analysis showed that 126 genes were differentially expressed in monoclonal gammopathy of undetermined significance, smoldering myeloma and multiple myeloma as compared to normal plasma cell. Interestingly, 17 and 9 out of the 126 significant differentially expressed genes were small nucleolar RNA molecules and zinc finger proteins. Several proapoptotic genes (AKT1 and AKT2) were down-regulated and antiapoptotic genes (APAF1 and BCL2L1) were up-regulated in multiple myeloma, both symptomatic and asymptomatic, compared to monoclonal gammopathy of undetermined significance. When we looked for those genes progressively modulated through the evolving stages of monoclonal gammopathies, eight snoRNA showed a progressive increase while APAF1, VCAN and MEGF9 exhibited a progressive downregulation. In conclusion, our data show that although monoclonal gammopathy of undetermined significance, smoldering myeloma and multiple myeloma are not clearly distinguishable groups according to their gene expression profiling, several signaling pathways and genes were significantly deregulated at different steps of the transformation process.