@article{814a8eb44d2f4f21a7f1884bd42d58bd,
title = "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",
abstract = "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.",
keywords = "Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Murine-Derived, Antineoplastic Combined Chemotherapy Protocols, B-Lymphocyte Subsets, Cohort Studies, Cyclophosphamide, Doxorubicin, Female, Gene Expression Regulation, Neoplastic, Humans, International Cooperation, Lymphocyte Activation, Lymphoma, Large B-Cell, Diffuse, Male, Middle Aged, Prednisone, Prognosis, Proto-Oncogene Proteins c-bcl-2, Proto-Oncogene Proteins c-myc, Retrospective Studies, Risk Factors, Survival Analysis, Transcriptome, Vincristine",
author = "Shimin Hu and Xu-Monette, {Zijun Y} and Alexander Tzankov and Tina Green and Lin Wu and Aarthi Balasubramanyam and Wei-min Liu and Carlo Visco and Yong Li and Miranda, {Roberto N} and Santiago Montes-Moreno and Karen Dybk{\ae}r and April Chiu and Attilio Orazi and Youli Zu and Govind Bhagat and Richards, {Kristy L} and Hsi, {Eric D} and Choi, {William W L} and Xiaoying Zhao and {van Krieken}, {J Han} and Qin Huang and Jooryung Huh and Weiyun Ai and Maurilio Ponzoni and Ferreri, {Andr{\'e}s J M} and Fan Zhou and Slack, {Graham W} and Gascoyne, {Randy D} and Meifeng Tu and Daina Variakojis and Weina Chen and Go, {Ronald S} and Piris, {Miguel A} and Michael M{\o}ller and Medeiros, {L Jeffrey} and Young, {Ken H}",
year = "2013",
month = may,
day = "16",
doi = "10.1182/blood-2012-10-460063",
language = "English",
volume = "121",
pages = "4021--31; quiz 4250",
journal = "Blood",
issn = "0006-4971",
publisher = "AMER SOC HEMATOLOGY",
number = "20",
}