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.
Type
Journal articleSubject
B-Lymphocyte SubsetsHumans
Cyclophosphamide
Vincristine
Doxorubicin
Prednisone
Proto-Oncogene Proteins c-myc
Proto-Oncogene Proteins c-bcl-2
Antineoplastic Combined Chemotherapy Protocols
Prognosis
Risk Factors
Survival Analysis
Retrospective Studies
Cohort Studies
Lymphocyte Activation
Gene Expression Regulation, Neoplastic
International Cooperation
Adult
Aged
Aged, 80 and over
Middle Aged
Female
Male
Lymphoma, Large B-Cell, Diffuse
Antibodies, Monoclonal, Murine-Derived
Transcriptome
Rituximab
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https://hdl.handle.net/10161/19329Published Version (Please cite this version)
10.1182/blood-2012-10-460063Publication Info
Hu, Shimin; Xu-Monette, Zijun Y; Tzankov, Alexander; Green, Tina; Wu, Lin; Balasubramanyam,
Aarthi; ... Young, Ken H (2013). 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.
Blood, 121(20). pp. 4021-4250. 10.1182/blood-2012-10-460063. Retrieved from https://hdl.handle.net/10161/19329.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Zijun Yidan Xu-Monette
Assistant Professor in Pathology
My research efforts have been focused on identifying prognostic and therapeutic biomarkers
in B-cell lymphoma. My research interests also include investigation of molecular
and immune mechanisms underlying the poor clinical outcomes of lymphoma, the pathogenesis
and evolution of drug resistant clones, and development of novel therapies for aggressive
B-cell lymphoma.
Ken H Young
Professor of Pathology
I am a clinically-oriented diagnostic physician with clinical expertise in the pathologic
diagnosis of hematologic cancers including tumors of the bone marrow, lymphoid tissue,
spleen and pre-malignant hematologic conditions. Another area of interest is blood
cancer classification with molecular and genetic profiling. In my research program,
we focus on molecular mechanisms of tumor progression, cell-of-origin, biomarkers,
and novel therapeutic strategies in lymphoma, myeloma and leukemia. In
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