Research Papers:
Clinical and biological significance of de novo CD5+ diffuse large B-cell lymphoma in Western countries
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Abstract
Zijun Y. Xu-Monette1,*, Meifeng Tu2,*, Kausar J. Jabbar1, Xin Cao1, Alexandar Tzankov3, Carlo Visco4, Qingqing Cai1, Santiago Montes-Moreno5, Yuji An1, Karen Dybkaer6, April Chiu7, Attilio Orazi8, Youli Zu9, Govind Bhagat10, Kristy L. Richards11, Eric D. Hsi12, William W.L. Choi13, J. Han van Krieken14, Jooryung Huh15, Maurilio Ponzoni16, Andrés J.M. Ferreri16, Xiaoying Zhao17, Michael B. Møller18, John P. Farnen19, Jane N. Winter20, Miguel A. Piris5, Roberto N. Miranda1, L. Jeffrey Medeiros1 and Ken H. Young1,21
1 Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
2 Peking University Cancer Hospital and Institute, Beijing, China
3 University Hospital, Basel, Switzerland
4 San Bortolo Hospital, Vicenza, Italy
5 Hospital Universitario Marques de Valdecilla, Santander, Spain
6 Aalborg University Hospital, Aalborg, Denmark
7 Memorial Sloan-Kettering Cancer Center, New York, NY, USA
8 Weill Medical College of Cornell University, New York, NY, USA
9 The Methodist Hospital, Houston, TX, USA
10 Columbia University Medical Center and New York Presbyterian Hospital, New York, NY, USA
11 University of North Carolina School of Medicine, Chapel Hill, NC, USA
12 Cleveland Clinic, Cleveland, OH, USA
13 University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong, China
14 Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
15 Asan Medical Center, Ulsan University College of Medicine, Seoul, Korea
16 San Raffaele H. Scientific Institute, Milan, Italy
17 Zhejiang University School of Medicine, Second University Hospital, Hangzhou, China
18 Odense University Hospital, Odense, Denmark
19 Gundersen Lutheran Health System, La Crosse, WI, USA
20 Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
21 The University of Texas School of Medicine, Graduate School of Biomedical Sciences, Houston, Texas, USA
* These authors made equal contributions to this work
Correspondence to:
Ken H. Young, email:
Keywords: ABC, BCL2, CD5, diffuse large B-cell lymphoma, NF-κB
Received: December 29, 2014 Accepted: January 02, 2015 Published: March 08, 2015
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.
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