The molecular classification of multiple myeloma
The molecular classification of multiple myeloma
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DOI：
10.1182/blood-2005-11-013458
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发表时间：
2006-09-15
期刊：
影响因子：
20.3
通讯作者：
Shaughnessy, John D., Jr.
中科院分区：
文献类型：
--
作者：
Zhan, Fenghuang;Huang, Yongsheng;Shaughnessy, John D., Jr.
为了更好地确定多发性骨髓瘤(MM)的分子基础，我们对414名接受高度封闭治疗和串联干细胞移植的新诊断患者的CD138富集浆细胞中的mRNA表达谱进行了无监督的分层聚类。有7种疾病亚型受到已知遗传损伤的强烈影响，如c-MAF-和MAFB-，CCND1-和CCND3-，以及MMSET激活的易位和超二倍体。在c-MAF和MAFB激活以及CCND1和CCND3激活的病例中观察到共同的基因特征，后者由两个亚群组成，一个亚群的特征是早期B细胞标记CD20和PAX5的表达，这表明基因同源基因解除了对共同通路的调控。局灶性骨病的发生率较低，这与另一新亚组的显著差异和增殖相关基因的表达增加。由其他6个亚组中每一个亚组的不同部分组成，增殖亚组在复发时占主导地位，这表明这一特征与疾病进展有关。增殖组和MMSET-棘波组的特点是定位于染色体1q的基因显著过表达，与其他组相比，两者的预后都较差。有主要髓系基因表达特征的病例子集，排除在侧写分析之外，与那些没有这种特征的病例相比，具有更有利的基线特征和更好的预后。
To better define the molecular basis of multiple myeloma (MM), we performed unsupervised hierarchic clustering of mRNA expression profiles in CD138-enriched plasma cells from 414 newly diagnosed patients who went on to receive high-close therapy and tandem stem cell transplants. Seven disease subtypes were validated that were strongly influenced by known genetic lesions, such as c-MAF- and MAFB-, CCND1- and CCND3-, and MMSET-activating translocations and hyperdiploidy. Indicative of the deregulation of common pathways by gene orthologs, common gene signatures were observed in cases with c-MAF and MAFB activation and CCND1 and CCND3 activation, the latter consisting of 2 subgroups, one characterized by expression of the early B-cell markers CD20 and PAX5. A low incidence of focal bone disease distinguished one and increased expression of proliferation-associated genes of another novel subgroup. Comprising varying fractions of each of the other 6 subgroups, the proliferation subgroup dominated at relapse, suggesting that this signature is linked to disease progression. Proliferation and MMSET-spike groups were characterized by significant overexpression of genes mapping to chromosome 1q, and both exhibited a poor prognosis relative to the other groups. A subset of cases with a predominating myeloid gene expression signature, excluded from the profiling analyses, had more favorable baseline characteristics and superior prognosis to those lacking this signature.