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题目:: The molecular classification of multiple myeloma.
作者:: Zhan(Fenghuang),Huang(Yongsheng),Colla(Simona),Stewart(James P),Hanamura(Ichiro),Gupta(Sushil),Epstein(Joshua),Yaccoby(Shmuel),Sawyer(Jeffrey),Burington(Bart),Anaissie(Elias),Hollmig(Klaus),Pineda-Roman(Mauricio),Tricot(Guido),van Rhee(Frits),Walker(Ronald),Zangari(Maurizio),Crowley(John),Barlogie(Bart),Shaughnessy(John D)
状态:: 发布时间2006-09-07 , 更新时间 2016-10-19
期刊:: Blood
摘要:: 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.
语言:: eng
DOI:

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