Hu, Shimin5; Xu-Monette, Zijun Y5; Tzankov, Alexander5; Green, Tina6; Wu, Lin5; Balasubramanyam, Aarthi5; Liu, Wei-min5; Visco, Carlo5; Li, Yong5; Miranda, Roberto N5; Montes-Moreno, Santiago5; Dybkær, Karen7; Chiu, April5; Orazi, Attilio5; Zu, Youli5; Bhagat, Govind5; Richards, Kristy L5; Hsi, Eric D5; Choi, William W L5; Zhao, Xiaoying5; van Krieken, J Han5; Huang, Qin5; Huh, Jooryung5; Ai, Weiyun5; Ponzoni, Maurilio5; Ferreri, Andrés J M5; Zhou, Fan8; Slack, Graham W5; Gascoyne, Randy D5; Tu, Meifeng5; Variakojis, Daina5; Chen, Weina5; Go, Ronald S5; Piris, Miguel A5; Møller, Michael9; Medeiros, L Jeffrey5; Young, Ken H5
1 The Faculty of Medicine, Aalborg University, VBN2 Aalborg University Hospital, The Faculty of Medicine, Aalborg University, VBN3 Klinik Medicin, The Faculty of Medicine, Aalborg University, VBN4 Blodsygdomme (Hæmatologi), The Faculty of Medicine, Aalborg University, VBN5 unknown6 Patologi7 Department of Clinical Medicine, The Faculty of Medicine, Aalborg University, VBN8 The Faculty of Engineering and Science, Aalborg University, VBN9 Klinisk Institut
a report from The International DLBCL Rituximab-CHOP Consortium Program
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.