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.
Highlights
CD5 is a cell surface glycoprotein typically expressed on normal and neoplastic T- cells, as well as on a subset of normal naïve B-cells and lymphoma cells, mainly in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma [1,2,3,4]
CD5+ diffuse large B-cell lymphoma (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
This study shows the distinctive clinical and biological features of CD5+ DLBCL patients in Western countries and underscores important pathways with therapeutic implications
Summary
CD5 is a cell surface glycoprotein typically expressed on normal and neoplastic T- cells, as well as on a subset of normal naïve B-cells and lymphoma cells, mainly in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma [1,2,3,4]. CD5 has an immunoreceptor tyrosine inhibitory motif and functionally inhibits the T-cell response [5,6] and B-cell receptor (BCR) signaling-mediated apoptosis, probably by recruiting the SH2 domain-containing protein tyrosine phosphatase-1 (SHP-1) after being phosphorylated by Lyn [7,8]. CD5 inhibits signaling downstream of the BCR pathway, including the calcium response and interleukin-2 (IL2) production whereas augments BCR-mediated IL10 production, an antiinflammatory cytokine and a survival factor for B-cells [9,10]. CD5 has been found to be expressed, albeit rarely, in de novo diffuse large B-cell lymphoma (DLBCL). Large-scale studies of de novo CD5+ DLBCL have been conducted only in Japan, with a reported frequency of 5 to 22% of all DLBCL [13,14,15,16,17,18,19,20]. CD5+ DLBCL are associated with centroblastic morphology (rarely immunoblastic), Bcl-2 overexpression, and nongerminal center B-cell (non-GCB) subtype [16,19]
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