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

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

doi:10.1158/1078-0432.CCR-11-0267

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

Javeed Iqbal, Paul N. Meyer, Lynette M. Smith, Nathalie A. Johnson, Julie M. Vose, Timothy C. Greiner, Joseph M. Connors, Louis M. Staudt, Lisa Rimsza, Elaine Jaffe, …

Clinical cancer research, Vol.17(24), pp.7785-7795

12/15/2011

DOI: 10.1158/1078-0432.CCR-11-0267

PMCID: PMC7394278

PMID: 21933893

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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-alpha) signature in BCL2 (-)GCB-DLBCL, whereas T-FH 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. (C) 2011 AACR.

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Title: Subtitle: BCL2 Predicts Survival in Germinal Center B-cell-like Diffuse Large B-cell Lymphoma Treated with CHOP-like Therapy and Rituximab
Creators: Javeed Iqbal - Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA
Paul N. Meyer - Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA
Lynette M. Smith - Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Biostat, Omaha, NE USA
Nathalie A. Johnson - British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 4E6, Canada
Julie M. Vose - Univ Nebraska Med Ctr, Dept Hematol Oncol, Omaha, NE USA
Timothy C. Greiner - Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA
Joseph M. Connors - British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 4E6, Canada
Louis M. Staudt - NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
Lisa Rimsza - University of Arizona
Elaine Jaffe - NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
Andreas Rosenwald - University of Würzburg
German Ott - Fischer (Germany)
Jan Delabie - University of Oslo
Elias Campo - Univ Barcelona, Hosp Clin, Barcelona, Spain
Rita M. Braziel - Oregon Hlth, Clin Pathol, Portland, OR USA
James R. Cook - Cleveland Clin, Pathol & Lab Med Inst, Cleveland, OH 44106 USA
Raymond R. Tubbs - Cleveland Clin, Pathol & Lab Med Inst, Cleveland, OH 44106 USA
Randy D. Gascoyne - British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 4E6, Canada
James O. Armitage - Univ Nebraska Med Ctr, Dept Hematol Oncol, Omaha, NE USA
Dennis D. Weisenburger - Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA
Wing C. Chan - Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA
Resource Type: Journal article
Publication Details: Clinical cancer research, Vol.17(24), pp.7785-7795
DOI: 10.1158/1078-0432.CCR-11-0267
PMID: 21933893
PMCID: PMC7394278
NLM abbreviation: Clin Cancer Res
ISSN: 1078-0432
eISSN: 1557-3265
Publisher: Amer Assoc Cancer Research
Number of pages: 11
Grant note: 5U01/CA114778 / NCI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
Language: English
Date published: 12/15/2011
Academic Unit: Pathology
Record Identifier: 9984823121002771

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