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

// Zijun Y. Xu-Monette 1,* , Meifeng Tu 2,* , Kausar J. Jabbar 1 , Xin Cao 1 , Alexandar Tzankov 3 , Carlo Visco 4 , Qingqing Cai 1 , Santiago Montes-Moreno 5 , Yuji An 1 , Karen Dybkaer 6 , April Chiu 7 , Attilio Orazi 8 , Youli Zu 9 , Govind Bhagat 10 , Kristy L. Richards 11 , Eric D. Hsi 12 , William W.L. Choi 13 , J. Han van Krieken 14 , Jooryung Huh 15 , Maurilio Ponzoni 16 , Andres J.M. Ferreri 16 , Xiaoying Zhao 17 , Michael B. Moller 18 , John P. Farnen 19 , Jane N. Winter 20 , Miguel A. Piris 5 , Roberto N. Miranda 1 , L. Jeffrey Medeiros 1 and Ken H. Young 1,21 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.