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. 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

doi:10.1056/NEJMoa0802885

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 journal › Article › peer-review

1122 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 language	English (US)
Pages (from-to)	2313-2323
Number of pages	11
Journal	New England Journal of Medicine
Volume	359
Issue number	22
DOIs	https://doi.org/10.1056/NEJMoa0802885
State	Published - Nov 27 2008

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Medicine(all)

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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., ... 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, T. P.; Rimsza, L. 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 journal › Article › peer-review

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, 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, T. P. ; Rimsza, L. 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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title = "Stromal gene signatures in large-B-cell lymphomas",

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, {T. P.} and Rimsza, {L. 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, T. P.

AU - Rimsza, L. 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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VL - 359

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EP - 2323

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

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