Stromal gene signatures in large-B-cell lymphomas

G. Lenz, 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. ConnorsG. 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

Research output: Contribution to journalArticlepeer-review

1107 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2313-2323
Number of pages11
JournalNew England Journal of Medicine
Volume359
Issue number22
DOIs
StatePublished - Nov 27 2008

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Stromal gene signatures in large-B-cell lymphomas'. Together they form a unique fingerprint.

Cite this