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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.

dc.contributor.author Young, Ken
dc.contributor.author Hu, Shimin
dc.contributor.author Xu-Monette, Zijun Y
dc.contributor.author Tzankov, Alexander
dc.contributor.author Green, Tina
dc.contributor.author Wu, Lin
dc.contributor.author Balasubramanyam, Aarthi
dc.contributor.author Liu, Wei-min
dc.contributor.author Visco, Carlo
dc.contributor.author Li, Yong
dc.contributor.author Miranda, Roberto N
dc.contributor.author Montes-Moreno, Santiago
dc.contributor.author Dybkaer, Karen
dc.contributor.author Chiu, April
dc.contributor.author Orazi, Attilio
dc.contributor.author Zu, Youli
dc.contributor.author Bhagat, Govind
dc.contributor.author Richards, Kristy L
dc.contributor.author Hsi, Eric D
dc.contributor.author Choi, William WL
dc.contributor.author Zhao, Xiaoying
dc.contributor.author van Krieken, J Han
dc.contributor.author Huang, Qin
dc.contributor.author Huh, Jooryung
dc.contributor.author Ai, Weiyun
dc.contributor.author Ponzoni, Maurilio
dc.contributor.author Ferreri, Andrés JM
dc.contributor.author Zhou, Fan
dc.contributor.author Slack, Graham W
dc.contributor.author Gascoyne, Randy D
dc.contributor.author Tu, Meifeng
dc.contributor.author Variakojis, Daina
dc.contributor.author Chen, Weina
dc.contributor.author Go, Ronald S
dc.contributor.author Piris, Miguel A
dc.contributor.author Møller, Michael B
dc.contributor.author Medeiros, L Jeffrey
dc.date.accessioned 2019-09-21T21:09:37Z
dc.date.available 2019-09-21T21:09:37Z
dc.date.issued 2013-05
dc.identifier blood-2012-10-460063
dc.identifier.issn 0006-4971
dc.identifier.issn 1528-0020
dc.identifier.uri https://hdl.handle.net/10161/19329
dc.description.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.
dc.language eng
dc.publisher American Society of Hematology
dc.relation.ispartof Blood
dc.relation.isversionof 10.1182/blood-2012-10-460063
dc.subject B-Lymphocyte Subsets
dc.subject Humans
dc.subject Cyclophosphamide
dc.subject Vincristine
dc.subject Doxorubicin
dc.subject Prednisone
dc.subject Proto-Oncogene Proteins c-myc
dc.subject Proto-Oncogene Proteins c-bcl-2
dc.subject Antineoplastic Combined Chemotherapy Protocols
dc.subject Prognosis
dc.subject Risk Factors
dc.subject Survival Analysis
dc.subject Retrospective Studies
dc.subject Cohort Studies
dc.subject Lymphocyte Activation
dc.subject Gene Expression Regulation, Neoplastic
dc.subject International Cooperation
dc.subject Adult
dc.subject Aged
dc.subject Aged, 80 and over
dc.subject Middle Aged
dc.subject Female
dc.subject Male
dc.subject Lymphoma, Large B-Cell, Diffuse
dc.subject Antibodies, Monoclonal, Murine-Derived
dc.subject Transcriptome
dc.subject Rituximab
dc.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.
dc.type Journal article
dc.date.updated 2019-09-21T21:09:36Z
pubs.begin-page 4021
pubs.end-page 4250
pubs.issue 20
pubs.organisational-group School of Medicine
pubs.organisational-group Duke
pubs.organisational-group Pathology
pubs.organisational-group Clinical Science Departments
pubs.publication-status Published
pubs.volume 121


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