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, Thomas P Miller, Lisa 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 journalArticle

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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

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B-Cell Lymphoma
Lymphoma, Large B-Cell, Diffuse
Survival
Genes
Transcriptome
Vascular Tissue Neoplasms
Gene Expression
Germinal Center
Tumor Microenvironment
Vincristine
Prednisone
Combination Drug Therapy
Doxorubicin
Cyclophosphamide
Extracellular Matrix
Fibrosis
B-Lymphocytes
Biopsy
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Lenz, G., Wright, G., Dave, S. S., Xiao, W., Powell, J., Zhao, H., ... Staudt, L. M. (2008). Stromal gene signatures in large-B-cell lymphomas. New England Journal of Medicine, 359(22), 2313-2323. https://doi.org/10.1056/NEJMoa0802885

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

In: New England Journal of Medicine, Vol. 359, No. 22, 27.11.2008, p. 2313-2323.

Research output: Contribution to journalArticle

Lenz, G, Wright, G, Dave, SS, Xiao, W, Powell, J, Zhao, H, Xu, W, Tan, B, Goldschmidt, N, Iqbal, J, Vose, J, Bast, M, Fu, K, Weisenburger, DD, Greiner, TC, Armitage, JO, Kyle, A, May, L, Gascoyne, RD, Connors, JM, Troen, G, Holte, H, Kvaloy, S, Dierickx, D, Verhoef, G, Delabie, J, Smeland, EB, Jares, P, Martinez, A, Lopez-Guillermo, A, Montserrat, E, Campo, E, Braziel, RM, Miller, TP, Rimsza, LM, Cook, JR, Pohlman, B, Sweetenham, J, Tubbs, RR, Fisher, RI, Hartmann, E, Rosenwald, A, Ott, G, Muller-Hermelink, HK, Wrench, D, Lister, TA, Jaffe, ES, Wilson, WH, Chan, WC & Staudt, LM 2008, 'Stromal gene signatures in large-B-cell lymphomas', New England Journal of Medicine, vol. 359, no. 22, pp. 2313-2323. https://doi.org/10.1056/NEJMoa0802885
Lenz G, Wright G, Dave SS, Xiao W, Powell J, Zhao H et al. Stromal gene signatures in large-B-cell lymphomas. New England Journal of Medicine. 2008 Nov 27;359(22):2313-2323. https://doi.org/10.1056/NEJMoa0802885
Lenz, G. ; Wright, G. ; Dave, S. S. ; Xiao, W. ; Powell, J. ; Zhao, H. ; Xu, W. ; Tan, B. ; Goldschmidt, N. ; Iqbal, J. ; Vose, J. ; Bast, M. ; Fu, K. ; Weisenburger, D. D. ; Greiner, T. C. ; Armitage, J. O. ; Kyle, A. ; May, L. ; Gascoyne, R. D. ; Connors, J. M. ; Troen, G. ; Holte, H. ; Kvaloy, S. ; Dierickx, D. ; Verhoef, G. ; Delabie, J. ; Smeland, E. B. ; Jares, P. ; Martinez, A. ; Lopez-Guillermo, A. ; Montserrat, E. ; Campo, E. ; Braziel, R. M. ; Miller, Thomas P ; Rimsza, Lisa M ; Cook, J. R. ; Pohlman, B. ; Sweetenham, J. ; Tubbs, R. R. ; Fisher, R. I. ; Hartmann, E. ; Rosenwald, A. ; Ott, G. ; Muller-Hermelink, H. K. ; Wrench, D. ; Lister, T. A. ; Jaffe, E. S. ; Wilson, W. H. ; Chan, W. C. ; Staudt, L. M. / Stromal gene signatures in large-B-cell lymphomas. In: New England Journal of Medicine. 2008 ; Vol. 359, No. 22. pp. 2313-2323.
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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.",
author = "G. Lenz and G. Wright and Dave, {S. S.} and W. Xiao and J. Powell and H. Zhao and W. Xu and B. Tan and N. Goldschmidt and J. Iqbal and J. Vose and M. Bast and K. Fu and Weisenburger, {D. D.} and Greiner, {T. C.} and Armitage, {J. O.} and A. Kyle and L. May and Gascoyne, {R. D.} and Connors, {J. M.} and G. Troen and H. Holte and S. Kvaloy and D. Dierickx and G. Verhoef and J. Delabie and Smeland, {E. B.} and P. Jares and A. Martinez and A. Lopez-Guillermo and E. Montserrat and E. Campo and Braziel, {R. M.} and Miller, {Thomas P} and Rimsza, {Lisa M} and Cook, {J. R.} and B. Pohlman and J. Sweetenham and Tubbs, {R. R.} and Fisher, {R. I.} and E. Hartmann and A. Rosenwald and G. Ott and Muller-Hermelink, {H. K.} and D. Wrench and Lister, {T. A.} and Jaffe, {E. S.} and Wilson, {W. H.} and Chan, {W. C.} and Staudt, {L. M.}",
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T1 - Stromal gene signatures in large-B-cell lymphomas

AU - Lenz, G.

AU - Wright, G.

AU - Dave, S. S.

AU - Xiao, W.

AU - Powell, J.

AU - Zhao, H.

AU - Xu, W.

AU - Tan, B.

AU - Goldschmidt, N.

AU - Iqbal, J.

AU - Vose, J.

AU - Bast, M.

AU - Fu, K.

AU - Weisenburger, D. D.

AU - Greiner, T. C.

AU - Armitage, J. O.

AU - Kyle, A.

AU - May, L.

AU - Gascoyne, R. D.

AU - Connors, J. M.

AU - Troen, G.

AU - Holte, H.

AU - Kvaloy, S.

AU - Dierickx, D.

AU - Verhoef, G.

AU - Delabie, J.

AU - Smeland, E. B.

AU - Jares, P.

AU - Martinez, A.

AU - Lopez-Guillermo, A.

AU - Montserrat, E.

AU - Campo, E.

AU - Braziel, R. M.

AU - Miller, Thomas P

AU - Rimsza, Lisa M

AU - Cook, J. R.

AU - Pohlman, B.

AU - Sweetenham, J.

AU - Tubbs, R. R.

AU - Fisher, R. I.

AU - Hartmann, E.

AU - Rosenwald, A.

AU - Ott, G.

AU - Muller-Hermelink, H. K.

AU - Wrench, D.

AU - Lister, T. A.

AU - Jaffe, E. S.

AU - Wilson, W. H.

AU - Chan, W. C.

AU - Staudt, L. M.

PY - 2008/11/27

Y1 - 2008/11/27

N2 - 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.

AB - 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.

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DO - 10.1056/NEJMoa0802885

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JO - New England Journal of Medicine

JF - New England Journal of Medicine

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