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. WeisenburgerWing C. Chan

Research output: Contribution to journalArticlepeer-review

121 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)7785-7795
Number of pages11
JournalClinical Cancer Research
Volume17
Issue number24
DOIs
StatePublished - Dec 15 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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