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 Ponzoni & 9 others 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

Research output: Contribution to journalArticle

32 Citations (Scopus)

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

Fingerprint

Lymphoma, Large B-Cell, Diffuse
DNA-Binding Proteins
B-Lymphocytes
Gene Expression Profiling
Disease-Free Survival
Central Nervous System
Bone Marrow
T-Lymphocytes
Recurrence
Mutation
Survival

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., ... 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.

Clinical and biological significance of de novo CD5+ diffuse large B-cell lymphoma in Western countries. / Xu-Monette, Zijun Y.; Tu, Meifeng; Jabbar, Kausar J.; Cao, Xin; Tzankov, Alexandar; Visco, Carlo; Cai, Qingqing; Montes-Moreno, Santiago; An, Yuji; Dybkaer, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L.; Hsi, Eric D.; Choi, William W L; Van Krieken, J. Han; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andrés J M; Zhao, Xiaoying; Møller, Michael B.; Farnen, John P.; Winter, Jane N.; Piris, Miguel A.; Miranda, Roberto N.; Medeiros, L. Jeffrey; Young, Ken H.

In: Oncotarget, Vol. 6, No. 8, 2015, p. 5615-5633.

Research output: Contribution to journalArticle

Xu-Monette, ZY, Tu, M, Jabbar, KJ, Cao, X, Tzankov, A, Visco, C, Cai, Q, Montes-Moreno, S, An, Y, Dybkaer, K, Chiu, A, Orazi, A, Zu, Y, Bhagat, G, Richards, KL, Hsi, ED, Choi, WWL, Van Krieken, JH, Huh, J, Ponzoni, M, Ferreri, AJM, Zhao, X, Møller, MB, Farnen, JP, Winter, JN, Piris, MA, Miranda, RN, Medeiros, LJ & Young, KH 2015, 'Clinical and biological significance of de novo CD5+ diffuse large B-cell lymphoma in Western countries', Oncotarget, vol. 6, no. 8, pp. 5615-5633.
Xu-Monette ZY, Tu M, Jabbar KJ, Cao X, Tzankov A, Visco C et al. Clinical and biological significance of de novo CD5+ diffuse large B-cell lymphoma in Western countries. Oncotarget. 2015;6(8):5615-5633.
Xu-Monette, Zijun Y. ; Tu, Meifeng ; Jabbar, Kausar J. ; Cao, Xin ; Tzankov, Alexandar ; Visco, Carlo ; Cai, Qingqing ; Montes-Moreno, Santiago ; An, Yuji ; Dybkaer, Karen ; Chiu, April ; Orazi, Attilio ; Zu, Youli ; Bhagat, Govind ; Richards, Kristy L. ; Hsi, Eric D. ; Choi, William W L ; Van Krieken, J. Han ; Huh, Jooryung ; Ponzoni, Maurilio ; Ferreri, Andrés J M ; Zhao, Xiaoying ; Møller, Michael B. ; Farnen, John P. ; Winter, Jane N. ; Piris, Miguel A. ; Miranda, Roberto N. ; Medeiros, L. Jeffrey ; Young, Ken H. / Clinical and biological significance of de novo CD5+ diffuse large B-cell lymphoma in Western countries. In: Oncotarget. 2015 ; Vol. 6, No. 8. pp. 5615-5633.
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AU - Jabbar, Kausar J.

AU - Cao, Xin

AU - Tzankov, Alexandar

AU - Visco, Carlo

AU - Cai, Qingqing

AU - Montes-Moreno, Santiago

AU - An, Yuji

AU - Dybkaer, Karen

AU - Chiu, April

AU - Orazi, Attilio

AU - Zu, Youli

AU - Bhagat, Govind

AU - Richards, Kristy L.

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AU - Huh, Jooryung

AU - Ponzoni, Maurilio

AU - Ferreri, Andrés J M

AU - Zhao, Xiaoying

AU - Møller, Michael B.

AU - Farnen, John P.

AU - Winter, Jane N.

AU - Piris, Miguel A.

AU - Miranda, Roberto N.

AU - Medeiros, L. Jeffrey

AU - Young, Ken H.

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