多发性骨髓瘤
基因表达谱
乘客5人
生物
癌症研究
基因签名
基因表达
基因
免疫学
内科学
肿瘤科
B细胞
医学
遗传学
抗体
作者
Fenghuang Zhan,Yongsheng Huang,Simona Colla,James Stewart,Ichiro Hanamura,Sushil K. Gupta,Joshua Epstein,Shmuel Yaccoby,Jeffrey R. Sawyer,Bart Burington,Elias Anaissie,Klaus Hollmig,Mauricio Pineda‐Roman,Guido Tricot,Frits van Rhee,Ronald C. Walker,Maurizio Zangari,John Crowley,Bart Barlogie,John D. Shaughnessy
出处
期刊:Blood
[American Society of Hematology]
日期:2006-09-15
卷期号:108 (6): 2020-2028
被引量:957
标识
DOI:10.1182/blood-2005-11-013458
摘要
Abstract 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-dose 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.
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