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

Shimin Hu, Zijun Y. Xu-Monette, Alexander Tzankov, Tina Green, Lin Wu, Aarthi Balasubramanyam, Wei Min Liu, Carlo Visco, Yong Li, Roberto N. Miranda, Santiago Montes-Moreno, Karen Dybkaer, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L. Richards, Eric D. His, William W.L. Choi, Xiaoying ZhaoJ. Han Van Krieken, Qin Huang, Jooryung Huh, Weiyun Ai, Maurilio Ponzoni, Andrés J.M. Ferreri, Fan Zhou, Graham W. Slack, Randy D. Gascoyne, Meifeng Tu, Daina Variakojis, Weina Chen, Ronald S. Go, Miguel A. Piris, Michael B. Møller, L. Jeffrey Medeiros, Ken H. Young

Research output: Contribution to journalArticle

403 Scopus citations

Abstract

Diffuse large B-cell lymphoma (DLBCL) is stratified into prognostically favorable germinal centerB-cell (GCB)-like and unfavorable activated B-cell (ABC)-like subtypes based on gene expression signatures. In this study, weanalyzed 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, ismore 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.

Original languageEnglish (US)
Pages (from-to)4021-4031
Number of pages11
JournalBlood
Volume121
Issue number20
DOIs
StatePublished - May 16 2013

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Cite this

    Hu, S., 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., Bhagat, G., Richards, K. L., His, E. D., Choi, W. W. L., ... Young, K. 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), 4021-4031. https://doi.org/10.1182/blood-2012-10-460063