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 | |
| State | Published - Nov 27 2008 |
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ASJC Scopus subject areas
- Medicine(all)
Cite this
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 journal › Article
}
TY - JOUR
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.
UR - http://www.scopus.com/inward/record.url?scp=57149089307&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=57149089307&partnerID=8YFLogxK
U2 - 10.1056/NEJMoa0802885
DO - 10.1056/NEJMoa0802885
M3 - Article
C2 - 19038878
AN - SCOPUS:57149089307
VL - 359
SP - 2313
EP - 2323
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 22
ER -