期刊
ONCOTARGET
卷 6, 期 8, 页码 5615-5633出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3479
关键词
ABC; BCL2; CD5; diffuse large B-cell lymphoma; NF-kappa B
资金
- University of Texas MD Anderson Cancer Center Institutional Research Grant Award
- MD Anderson Lymphoma Specialized Programs of Research Excellence (SPORE) Research Development Program Award
- MD Anderson Myeloma SPORE Research Development Program Award
- MD Anderson Collaborative Research Funds with High-Throughput Molecular Diagnostics
- Gilead Pharmaceutical
- Adaptive Biotechnology
- Roche Molecular Systems
- National Cancer Institute
- National Institutes of Health [R01CA138688, R01CA187415, P50CA136411, P50CA142509]
- MD Anderson Cancer Center Support Grant [CA016672]
- Harold C. and Mary L. Daily Endowment Fellowships
- Shannon Timmins Fellowship for Leukemia Research Award
- Pathology Division Biomarker Fellowship Award
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-kappa B 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-kappa B 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.
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