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
Top Cited Papers
Open Access
- 15 May 2013
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 121 (20), 4021-4031
- https://doi.org/10.1182/blood-2012-10-460063
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.This publication has 47 references indexed in Scilit:
- Comprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma: a report from the International DLBCL Rituximab-CHOP Consortium Program StudyLeukemia, 2012
- The isotype of the BCR as a surrogate for the GCB and ABC molecular subtypes in diffuse large B-cell lymphomaLeukemia, 2011
- Immunohistochemical Methods for Predicting Cell of Origin and Survival in Patients With Diffuse Large B-Cell Lymphoma Treated With RituximabJournal of Clinical Oncology, 2011
- B-cell Lymphomas With Concurrent IGH-BCL2 and MYC Rearrangements Are Aggressive Neoplasms With Clinical and Pathologic Features Distinct From Burkitt Lymphoma and Diffuse Large B-cell LymphomaThe American Journal of Surgical Pathology, 2010
- Lymphomas with concurrent BCL2 and MYC translocations: the critical factors associated with survivalBlood, 2009
- Prognostic impact of activated B-cell focused classification in diffuse large B-cell lymphoma patients treated with R-CHOPLaboratory Investigation, 2009
- Mutations of multiple genes cause deregulation of NF-κB in diffuse large B-cell lymphomaNature, 2009
- Bcl‐2 but not FOXP1, is an adverse risk factor in immunochemotherapy‐treated non‐germinal center diffuse large B‐cell lymphomasEuropean Journal of Haematology, 2009
- Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathwaysProceedings of the National Academy of Sciences of the United States of America, 2008
- Distinct types of diffuse large B-cell lymphoma identified by gene expression profilingNature, 2000