Clinical and biological significance ofde novoCD5+ 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.

Evaluation of NF-κB subunit expression and signaling pathway activation demonstrates that p52 expression confers better outcome in germinal center B-cell-like diffuse large B-cell lymphoma in association with CD30 and BCL2 functions

“…Therapeutic agents targeting the NF-κB pathway have been introduced into the therapeutic regimen of patients with DLBCLs, and it is important to identify groups of patients for whom such therapy might be most appropriate or patient subsets who might not benefit. 43,44 Acknowledgments …”

Concordant bone marrow involvement of diffuse large B-cell lymphoma represents a distinct clinical and biological entity in the era of immunotherapy

“…28 The interpretation of TP53 mutations by gene sequencing, MYC and BCL2 rearrangements by fluorescence in situ hybridization analyses, and p53, CD5, BCL2, and MYC expression by IHC staining were based on published data. 17, 20, 22, 23 A cut-off value for a high Ki-67 index was considered to be 70%. GEP of specimens involved by DLBCL was performed and the COO classification was analyzed by GEP and the IHC algorithm based on Choi and Visco/Young’s algorithm methods.…”

Clinical and Biologic Significance of MYC Genetic Mutations in De Novo Diffuse Large B-cell Lymphoma

“…Details of Sanger sequencing for MYC gene (in all patients), functional studies of Myc mutants in vitro and in vivo , fluorescence in situ hybridization for MYC rearrangement detection (successful in 455 patients), and Myc expression evaluation by immunohistochemistry (successful in 556 patients) performed on tissue microarrays using formalin-fixed, paraffin-embedded samples are in the supplementary documents or have been described previously (1,4,29,31). …”