Clinical and biological significance of de novo CD5+ diffuse large B-cell lymphoma in Western countries

Zijun Y. Xu-Monette, Meifeng Tu, Kausar J. Jabbar, Xin Cao, Alexandar Tzankov, Carlo Visco, Qingqing Cai, Santiago Montes-Moreno, Yuji An, Karen Dybkaer, April Chiu, Attilio Orazi, Youli Zu, Govind Bhagat, Kristy L. Richards, Eric D. Hsi, William W.L. Choi, J. Han Van Krieken, Jooryung Huh, Maurilio PonzoniAndrés J.M. Ferreri, Xiaoying Zhao, Michael B. Møller, John P. Farnen, Jane N. Winter, Miguel A. Piris, Roberto N. Miranda, L. Jeffrey Medeiros, Ken H. Young*

*Corresponding author for this work

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

CD5 is a pan-T-cell surface marker and is rarely expressed in diffuse large B-cell lymphoma (DLBCL). Large-scale studies of de novo CD5+ DLBCL are lacking in Western countries. In this study by the DLBCL Rituximab-CHOP Consortium, CD5 was expressed in 5.5% of 879 DLBCL patients from Western countries. CD5+ DLBCL was associated with higher frequencies of > 1 ECOG performance status, bone marrow involvement, central nervous system relapse, activated B-cell-like subtype, Bcl-2 overexpression, and STAT3 and NF-κB activation, whereas rarely expressed single-stranded DNA-binding protein 2 (SSBP2), CD30 or had MYC mutations. With standard R-CHOP chemotherapy, CD5+ DLBCL patients had significantly worse overall survival (median, 25.3 months vs. not reached, P < .0001) and progression-free survival (median, 21.3 vs. 85.8 months, P < .0001) than CD5- DLBCL patients, which was independent of Bcl-2, STAT3, NF-κB and the International Prognostic Index. Interestingly, SSBP2 expression abolished the prognostic significance of CD5 expression, suggesting a tumor-suppressor role of SSBP2 for CD5 signaling. Gene-expression profiling demonstrated that B-cell receptor signaling dysfunction and microenvironment alterations are the important mechanisms underlying the clinical impact of CD5 expression. This study shows the distinctive clinical and biological features of CD5+ DLBCL patients in Western countries and underscores important pathways with therapeutic implications.

Original languageEnglish (US)
Pages (from-to)5615-5633
Number of pages19
JournalOncotarget
Volume6
Issue number8
DOIs
StatePublished - Jan 1 2015

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Keywords

  • ABC
  • BCL2
  • CD5
  • Diffuse large B-cell lymphoma
  • NF-κB

ASJC Scopus subject areas

  • Oncology

Cite this

Xu-Monette, Z. Y., Tu, M., Jabbar, K. J., Cao, X., Tzankov, A., Visco, C., Cai, Q., Montes-Moreno, S., An, Y., Dybkaer, K., Chiu, A., Orazi, A., Zu, Y., Bhagat, G., Richards, K. L., Hsi, E. D., Choi, W. W. L., Van Krieken, J. H., Huh, J., ... Young, K. H. (2015). Clinical and biological significance of de novo CD5+ diffuse large B-cell lymphoma in Western countries. Oncotarget, 6(8), 5615-5633. https://doi.org/10.18632/oncotarget.3479