MYC/BCL2 protein coexpression contributes to the inferior survival of activated B-cell subtype of diffuse large B-cell lymphoma and demonstrates high-risk gene expression signatures: a report from The International DLBCL Rituximab-CHOP Consortium Program.

Published

Journal Article

Diffuse large B-cell lymphoma (DLBCL) is stratified into prognostically favorable germinal center B-cell (GCB)-like and unfavorable activated B-cell (ABC)-like subtypes based on gene expression signatures. In this study, we analyzed 893 de novo DLBCL patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). We show that MYC/BCL2 protein coexpression occurred significantly more commonly in the ABC subtype. Patients with the ABC or GCB subtype of DLBCL had similar prognoses with MYC/BCL2 coexpression and without MYC/BCL2 coexpression. Consistent with the notion that the prognostic difference between the 2 subtypes is attributable to MYC/BCL2 coexpression, there is no difference in gene expression signatures between the 2 subtypes in the absence of MYC/BCL2 coexpression. DLBCL with MYC/BCL2 coexpression demonstrated a signature of marked downregulation of genes encoding extracellular matrix proteins, those involving matrix deposition/remodeling and cell adhesion, and upregulation of proliferation-associated genes. We conclude that MYC/BCL2 coexpression in DLBCL is associated with an aggressive clinical course, is more common in the ABC subtype, and contributes to the overall inferior prognosis of patients with ABC-DLBCL. In conclusion, the data suggest that MYC/BCL2 coexpression, rather than cell-of-origin classification, is a better predictor of prognosis in patients with DLBCL treated with R-CHOP.

Full Text

Duke Authors

Cited Authors

  • Hu, S; Xu-Monette, ZY; Tzankov, A; Green, T; Wu, L; Balasubramanyam, A; Liu, W-M; Visco, C; Li, Y; Miranda, RN; Montes-Moreno, S; Dybkaer, K; Chiu, A; Orazi, A; Zu, Y; Bhagat, G; Richards, KL; Hsi, ED; Choi, WWL; Zhao, X; van Krieken, JH; Huang, Q; Huh, J; Ai, W; Ponzoni, M; Ferreri, AJM; Zhou, F; Slack, GW; Gascoyne, RD; Tu, M; Variakojis, D; Chen, W; Go, RS; Piris, MA; Møller, MB; Medeiros, LJ; Young, KH

Published Date

  • May 16, 2013

Published In

Volume / Issue

  • 121 / 20

Start / End Page

  • 4021 - 4031

PubMed ID

  • 23449635

Pubmed Central ID

  • 23449635

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

Digital Object Identifier (DOI)

  • 10.1182/blood-2012-10-460063

Language

  • eng

Conference Location

  • United States