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

نویسندگان

  • 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 Ponzoni
  • Andrés 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
چکیده

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.

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عنوان ژورنال:

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2015