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 Journal Article
| Authors: | Hu, S. M.; Xu-Monette, Z. Y.; Tzankov, A.; Green, T.; Wu, L.; Balasubramanyam, A.; Liu, W. M.; Visco, C.; Li, Y.; Miranda, R. N.; Montes-Moreno, S.; Dybkaer, K.; Chiu, A.; Orazi, A.; Zu, Y. L.; Bhagat, G.; Richards, K. L.; Hsi, E. D.; Choi, W. W. L.; Zhao, X. Y.; van Krieken, J. H.; Huang, Q.; Huh, J.; Ai, W. Y.; Ponzoni, M.; Ferreri, A. J. M.; Zhou, F.; Slack, G. W.; Gascoyne, R. D.; Tu, M. F.; Variakojis, D.; Chen, W. N.; Go, R. S.; Piris, M. A.; Moller, M. B.; Medeiros, L. J.; Young, K. H. |
| Article 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: | cyclophosphamide; nf-kappa-b; plus; poor-prognosis; bcl-2 expression; distinct; prognostic impact; predicts survival; molecular subtypes; r-chop; t(14/18) |
| Journal Title: | Blood |
| Volume: | 121 |
| Issue: | 20 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2013-05-16 |
| Start Page: | 4021 |
| End Page: | 4031 |
| Language: | English |
| DOI: | 10.1182/blood-2012-10-460063 |
| ACCESSION: | WOS:000321871900006 |
| PROVIDER: | wos |
| PMCID: | PMC3709650 |
| PUBMED: | 23449635 |
| Notes: | --- - Article - "Source: Wos" |
