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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

American Society of Hematology
Publication Date
  • 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
  • Biology


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.

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