Clinical and biological significance of de novo CD5+ diffuse large B-cell lymphoma in Western countries Journal Article
| Authors: | Xu-Monette, Z. Y.; Tu, M.; Jabbar, K. J.; Cao, X.; Tzankov, A.; Visco, C.; Nagarajan, L.; Cai, Q.; Montes-Moreno, S.; An, Y.; Dybkaer, K.; Chiu, A.; Orazi, A.; Zu, Y.; Bhagat, G.; Richards, K. L.; Hsi, E. D.; Choi, W. W. L.; van Krieken, J. H.; Huh, J.; Ponzoni, M.; Ferreri, A. J. M.; Zhao, X.; Møller, M. B.; Farnen, J. P.; Winter, J. N.; Piris, M. A.; Miranda, R. N.; Medeiros, L. J.; Young, K. H. |
| Article Title: | Clinical and biological significance of de novo CD5+ diffuse large B-cell lymphoma in Western countries |
| 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. |
| Keywords: | signal transduction; adult; clinical article; controlled study; protein expression; unclassified drug; gene mutation; overall survival; clinical feature; doxorubicin; rituximab; protein function; antigen expression; protein bcl 2; stat3 protein; progression free survival; gene expression; relapse; cyclophosphamide; vincristine; cancer inhibition; prednisolone; bcl2; large cell lymphoma; cd5 antigen; oncogene myc; bone marrow disease; diffuse large b-cell lymphoma; cd30 antigen; central nervous system disease; international prognostic index; tumor microenvironment; nf-κb; single stranded dna binding protein; b lymphocyte receptor; western hemisphere; b lymphocyte activation; cancer prognosis; abc; human; male; female; article; cd5; single stranded dna binding protein 2 |
| Journal Title: | Oncotarget |
| Volume: | 6 |
| Issue: | 8 |
| ISSN: | 1949-2553 |
| Publisher: | Impact Journals |
| Date Published: | 2015-03-20 |
| Start Page: | 5615 |
| End Page: | 5633 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 25760242 |
| PMCID: | PMC4467390 |
| DOI: | 10.18632/oncotarget.3479 |
| DOI/URL: | |
| Notes: | Export Date: 4 May 2015 -- Source: Scopus |
