Literature DB >> 19038878

Stromal gene signatures in large-B-cell lymphomas.

G Lenz1, G Wright, S S Dave, W Xiao, J Powell, H Zhao, W Xu, B Tan, N Goldschmidt, J Iqbal, J Vose, M Bast, K Fu, D D Weisenburger, T C Greiner, J O Armitage, A Kyle, L May, R D Gascoyne, J M Connors, G Troen, H Holte, S Kvaloy, D Dierickx, G Verhoef, J Delabie, E B Smeland, P Jares, A Martinez, A Lopez-Guillermo, E Montserrat, E Campo, R M Braziel, T P Miller, L M Rimsza, J R Cook, B Pohlman, J Sweetenham, R R Tubbs, R I Fisher, E Hartmann, A Rosenwald, G Ott, H-K Muller-Hermelink, D Wrench, T A Lister, E S Jaffe, W H Wilson, W C Chan, L M Staudt.   

Abstract

BACKGROUND: The addition of rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or R-CHOP, has significantly improved the survival of patients with diffuse large-B-cell lymphoma. Whether gene-expression signatures correlate with survival after treatment of diffuse large-B-cell lymphoma is unclear.
METHODS: We profiled gene expression in pretreatment biopsy specimens from 181 patients with diffuse large-B-cell lymphoma who received CHOP and 233 patients with this disease who received R-CHOP. A multivariate gene-expression-based survival-predictor model derived from a training group was tested in a validation group.
RESULTS: A multivariate model created from three gene-expression signatures--termed "germinal-center B-cell," "stromal-1," and "stromal-2"--predicted survival both in patients who received CHOP and patients who received R-CHOP. The prognostically favorable stromal-1 signature reflected extracellular-matrix deposition and histiocytic infiltration. By contrast, the prognostically unfavorable stromal-2 signature reflected tumor blood-vessel density.
CONCLUSIONS: Survival after treatment of diffuse large-B-cell lymphoma is influenced by differences in immune cells, fibrosis, and angiogenesis in the tumor microenvironment. 2008 Massachusetts Medical Society

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Year:  2008        PMID: 19038878      PMCID: PMC9103713          DOI: 10.1056/NEJMoa0802885

Source DB:  PubMed          Journal:  N Engl J Med        ISSN: 0028-4793            Impact factor:   91.245


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