Gene expression profiling of plasma cell dyscrasias reveals molecular patterns associated with distinct IGH translocations in multiple myeloma
Gene expression profiling of plasma cell dyscrasias reveals molecular patterns associated with distinct IGH translocations in multiple myeloma
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DOI：
10.1038/sj.onc.1208447
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发表时间：
2005-04-07
期刊：
影响因子：
8
通讯作者：
Neri, A
中科院分区：
文献类型：
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作者：
Mattioli, M;Agnelli, L;Neri, A
多发性骨髓瘤(MM)是浆细胞营养不良的最常见形式，其特点是遗传损害和临床病程具有显著的异质性。它可能从癌前状态(未确定意义的单克隆性伽马病，MGUS)发展到髓外形式(浆细胞白血病，PCL)。为了深入了解浆细胞营养不良的分子特征，并探讨特定的遗传损伤对MM的生物学和临床异质性的贡献，我们利用DNA芯片技术分析了7例MGUS、39例MM和6例PCL患者的浆细胞基因表达谱。MMS在转录水平上表现出高度的异质性，而主要参与DNA代谢和增殖的基因表达的差异则将MGUS与PCL和大多数MM病例区分开来。多发性骨髓瘤患者的聚集性主要是由涉及免疫球蛋白重链基因的最常见易位引起的。已发现不同的基因表达模式与不同的病变有关：CCND2和参与细胞黏附途径的基因在MAF和MAFB解除调节的病例中过度表达，而在t(4；14)病例中上调的基因具有与细胞凋亡相关的功能。奇特之处。在t(11；14)患者中发现IL-6受体α亚单位下调。此外，我们确定了一组在具有侵袭性临床演变特征的MM患者亚组中特异表达的癌症胚系抗原，这一发现可能对患者分类和免疫治疗有意义。
Multiple myeloma (MM) is the most common form of plasma cell dyscrasia, characterized by a marked heterogeneity of genetic lesions and clinical course. It may develop from a premalignant condition (monoclonal gammopathy of undetermined significance, MGUS) or progress from intramedullary to extramedullary forms (plasma cell leukemia, PCL). To provide insights into the molecular characterization of plasma cell dyscrasias and to investigate the contribution of specific genetic lesions to the biological and clinical heterogeneity of MM, we analysed the gene expression profiles of plasma cells isolated from seven MGUS, 39MM and six PCL patients by means of DNA microarrays. MMs resulted highly heterogeneous at transcriptional level, whereas the differential expression of genes mainly involved in DNA metabolism and proliferation distinguished MGUS from PCLs and the majority of MM cases. The clustering of MM patients was mainly driven by the presence of the most recurrent translocations involving the immunoglobulin heavy-chain locus. Distinct gene expression patterns have been found to be associated with different lesions: the overexpression of CCND2 and genes involved in cell adhesion pathways was observed in cases with deregulated MAF and MAFB, whereas genes upregulated in cases with the t(4; 14) showed apoptosis-related functions. The peculiar. finding in patients with the t(11; 14) was the downregulation of the a-subunit of the IL-6 receptor. In addition, we identified a set of cancer germline antigens specifically expressed in a subgroup of MM patients characterized by an aggressive clinical evolution, a finding that could have implications for patient classification and immunotherapy.