The molecular classification of multiple myeloma

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 subtype...

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Vydáno v:Blood Ročník 108; číslo 6; s. 2020
Hlavní autoři: 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, Jr, John D
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 15.09.2006
Témata:
Chromosome Mapping
Cluster Analysis
Cyclin D
Cyclins - genetics
Data Interpretation, Statistical
Gene Expression Profiling - statistics & numerical data
Humans
Membrane Glycoproteins - genetics
Multiple Myeloma - classification
Multiple Myeloma - genetics
Multiple Myeloma - immunology
Oligonucleotide Array Sequence Analysis - statistics & numerical data
Plasma Cells - immunology
Prognosis
Proteoglycans - genetics
RNA, Messenger - genetics
RNA, Neoplasm - genetics
Syndecan-1
Syndecans
ISSN:0006-4971
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Shrnutí: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.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:0006-4971
DOI:10.1182/blood-2005-11-013458