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Iqbal, Javeed; Meyer, Paul N.; Smith, Lynette M.; Johnson, Nathalie A.; Vose, Julie M.; Greiner, Timothy C.; Connors, Joseph M.; Staudt, Louis M.; Rimsza, Lisa; Jaffe, Elaine; Rosenwald, Andreas; Ott, German; Delabie, Jan; Campo, Elias; Braziel, Rita M.; Cook, James R.; Tubbs, Raymond R.; Gascoyne, Randy D.; Armitage, James O.; Weisenburger, Dennis D.; Chan, Wing C.

BCL2 Predicts Survival in Germinal Center B-cell–like Diffuse Large B-cell Lymphoma Treated with CHOP-like Therapy and Rituximab

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  • Media type: E-Article
  • Title: BCL2 Predicts Survival in Germinal Center B-cell–like Diffuse Large B-cell Lymphoma Treated with CHOP-like Therapy and Rituximab
  • Contributor: Iqbal, Javeed; Meyer, Paul N.; Smith, Lynette M.; Johnson, Nathalie A.; Vose, Julie M.; Greiner, Timothy C.; Connors, Joseph M.; Staudt, Louis M.; Rimsza, Lisa; Jaffe, Elaine; Rosenwald, Andreas; Ott, German; Delabie, Jan; Campo, Elias; Braziel, Rita M.; Cook, James R.; Tubbs, Raymond R.; Gascoyne, Randy D.; Armitage, James O.; Weisenburger, Dennis D.; Chan, Wing C.
  • Published: American Association for Cancer Research (AACR), 2011
  • Published in: Clinical Cancer Research, 17 (2011) 24, Seite 7785-7795
  • Language: English
  • DOI: 10.1158/1078-0432.ccr-11-0267
  • ISSN: 1078-0432; 1557-3265
  • Origination:
  • Footnote:
  • Description: Abstract Purpose: We have previously shown the prognostic significance of BCL2 expression in the activated B-cell–like diffuse large B-cell lymphoma (ABC-DLBCL) patients treated with cyclophosphamide-Adriamycin-vincristine-prednisone (CHOP) or CHOP-like therapy. However, after the inclusion of rituximab (R) in the CHOP regimen, several conflicting observations about the prognostic value of BCL2 expression have been reported. Experimental Design: We evaluated the R-CHOP cohort of 221 DLBCL cases with gene expression profiling data. BCL2 protein (n = 169), mRNA (n = 221) expression, and t(14;18) (n = 144) were correlated with clinical outcome. The CHOP cohort (n = 181) was used for comparative analysis. Results: BCL2 protein expression has significant impact on overall survival (OS) and event-free survival (EFS) in DLBCL (OS, P = 0.009; EFS, P = 0.001) and GCB-DLBCL (OS, P = 0.03; EFS, P = 0.002) but not in ABC-DLBCL in the R-CHOP cohort. The survival differences for EFS in GCB-DLBCL were still observed in multivariate analysis. At the mRNA level, this correlation was observed in EFS in DLBCL (P = 0.006), but only a trend was observed in GCB-DLBCL (P = 0.09). The t(14;18) was detected in 34% of GCB-DLBCL but was not associated with significant differences in survival. Gene enrichment analysis identified significant enrichment of the DLBCL “stromal-1” signatures and hypoxia-inducible factor 1 (HIF1-α) signature in BCL2(−)GCB-DLBCL, whereas TFH cell signatures were enriched in BCL2(+)GCB-DLBCL. Conclusion: The prognostic significance of BCL2 has changed after inclusion of rituximab in the treatment protocol and is observed in the GCB-DLBCL rather than the ABC-DLBCL. Although rituximab has benefited patients in both DLBCL subgroups, the BCL2(+)GCB-DLBCL seems to receive less benefit from this treatment and may require other novel therapeutic intervention. Clin Cancer Res; 17(24); 7785–95. ©2011 AACR.
  • Access State: Open Access