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

Research output: Contribution to journalArticlepeer-review

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
Pages (from-to)5615-5633
Number of pages19
JournalOncotarget
Volume6
Issue number8
Publication statusPublished - 2015

Keywords

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

ASJC Scopus subject areas

  • Oncology

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