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Shaughnessy, John D.; Zhan, Fenghuang; Burington, Bart E.; Huang, Yongsheng; Colla, Simona; Hanamura, Ichiro; Stewart, James P.; Kordsmeier, Bob; Randolph, Christopher; Williams, David R.; Xiao, Yan; Xu, Hongwei; Epstein, Joshua; Anaissie, Elias; Krishna, Somashekar G.; Cottler-Fox, Michele; Hollmig, Klaus; Mohiuddin, Abid; Pineda-Roman, Mauricio; Tricot, Guido; van Rhee, Frits; Sawyer, Jeffrey; Alsayed, Yazan; Walker, Ronald; [...]

A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1

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  • Medientyp: E-Artikel
  • Titel: A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1
  • Beteiligte: Shaughnessy, John D.; Zhan, Fenghuang; Burington, Bart E.; Huang, Yongsheng; Colla, Simona; Hanamura, Ichiro; Stewart, James P.; Kordsmeier, Bob; Randolph, Christopher; Williams, David R.; Xiao, Yan; Xu, Hongwei; Epstein, Joshua; Anaissie, Elias; Krishna, Somashekar G.; Cottler-Fox, Michele; Hollmig, Klaus; Mohiuddin, Abid; Pineda-Roman, Mauricio; Tricot, Guido; van Rhee, Frits; Sawyer, Jeffrey; Alsayed, Yazan; Walker, Ronald; [...]
  • Erschienen: American Society of Hematology, 2007
  • Erschienen in: Blood, 109 (2007) 6, Seite 2276-2284
  • Sprache: Englisch
  • DOI: 10.1182/blood-2006-07-038430
  • ISSN: 0006-4971; 1528-0020
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: Abstract To molecularly define high-risk disease, we performed microarray analysis on tumor cells from 532 newly diagnosed patients with multiple myeloma (MM) treated on 2 separate protocols. Using log-rank tests of expression quartiles, 70 genes, 30% mapping to chromosome 1 (P < .001), were linked to early disease-related death. Importantly, most up-regulated genes mapped to chromosome 1q, and down-regulated genes mapped to chromosome 1p. The ratio of mean expression levels of up-regulated to down-regulated genes defined a high-risk score present in 13% of patients with shorter durations of complete remission, event-free survival, and overall survival (training set: hazard ratio [HR], 5.16; P < .001; test cohort: HR, 4.75; P < .001). The high-risk score also was an independent predictor of outcome endpoints in multivariate analysis (P < .001) that included the International Staging System and high-risk translocations. In a comparison of paired baseline and relapse samples, the high-risk score frequency rose to 76% at relapse and predicted short postrelapse survival (P < .05). Multivariate discriminant analysis revealed that a 17-gene subset could predict outcome as well as the 70-gene model. Our data suggest that altered transcriptional regulation of genes mapping to chromosome 1 may contribute to disease progression, and that expression profiling can be used to identify high-risk disease and guide therapeutic interventions.
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