Medizinische Klinik V, Universitaetsklinikum Heidelberg, Heidelberg, Germany.
Genes Chromosomes Cancer. 2010 Apr;49(4):333-41. doi: 10.1002/gcc.20745.
Multiple myeloma (MM) is proposed to consist of two main pathogenetic groups. Although hyperdiploid MM (HD) is characterized by multiple trisomies of odd chromosomes, in nonhyperdiploid MM (NHD), one of the recurrent primary immunoglobulin heavy chain (IGH) translocations and deletion of chromosome 13 can frequently be found. In this study, we analyzed gene-expression profiles of patients with previously untreated MM. Fifty-four genes were significantly differentially expressed between the two groups. NPM1 was upregulated in HD. The differential expression of 25 genes, including NPM1 and 13 ribosomal protein genes, was validated using a published gene expression data set. The overexpression of NPM1 in HD was further confirmed by quantitative real-time PCR and Western blotting. NPM1 was significantly overexpressed in HD as the result of a gain of chromosome 5. Insertions into exon 12 of NPM1 were not detected. NPM1 was localized to the nucleoli of MM cells. Furthermore, HD was associated with an overexpression of ribosomal protein genes, independent of their localization on the trisomic or other chromosomes. Our results indicate that the gain of chromosome 5 might play an important role in the pathogenesis of HD.
多发性骨髓瘤（MM）被认为由两个主要的发病机制群组成。虽然超二倍体 MM（HD）的特征是多个奇数染色体的三体，但在非超二倍体 MM（NHD）中，经常可以发现其中一种复发性主要免疫球蛋白重链（IGH）易位和 13 号染色体缺失。在这项研究中，我们分析了未经治疗的 MM 患者的基因表达谱。两组之间有 54 个基因的表达存在显著差异。NPM1 在 HD 中上调。使用已发表的基因表达数据集验证了包括 NPM1 和 13 个核糖体蛋白基因在内的 25 个基因的差异表达。通过定量实时 PCR 和 Western blot 进一步证实了 HD 中 NPM1 的过表达。NPM1 的过表达是由于获得了 5 号染色体。未检测到 NPM1 插入 12 外显子。NPM1 定位于 MM 细胞的核仁中。此外，HD 与核糖体蛋白基因的过度表达有关，而与它们在三体或其他染色体上的定位无关。我们的结果表明，5 号染色体的获得可能在 HD 的发病机制中起重要作用。
