Back to Search
Start Over
Prognostic impact of c-Rel nuclear expression and REL amplification and crosstalk between c-Rel and the p53 pathway in diffuse large B-cell lymphoma
- Source :
- Oncotarget; 23157; 23180; 1949-2553; 27; 6; ~Oncotarget~23157~23180~~~1949-2553~27~6~~
- Publication Year :
- 2015
-
Abstract
- Contains fulltext : 153743.pdf (publisher's version ) (Closed access)<br />Dysregulated NF-kappaB signaling is critical for lymphomagenesis. The regulation, function, and clinical relevance of c-Rel/NF-kappaB activation in diffuse large B-cell lymphoma (DLBCL) have not been well studied. In this study we analyzed the prognostic significance and gene-expression signature of c-Rel nuclear expression as surrogate of c-Rel activation in 460 patients with de novo DLBCL. Nuclear c-Rel expression, observed in 137 (26.3%) DLBCL patients frequently associated with extranoal origin, did not show significantly prognostic impact in the overall- or germinal center B-like-DLBCL cohort, likely due to decreased pAKT and Myc levels, up-regulation of FOXP3, FOXO3, MEG3 and other tumor suppressors coincided with c-Rel nuclear expression, as well as the complicated relationships between NF-kappaB members and their overlapping function. However, c-Rel nuclear expression correlated with significantly poorer survival in p63+ and BCL-2- activated B-cell-like-DLBCL, and in DLBCL patients with TP53 mutations. Multivariate analysis indicated that after adjusting clinical parameters, c-Rel positivity was a significantly adverse prognostic factor in DLBCL patients with wild type TP53. Gene expression profiling suggested dysregulations of cell cycle, metabolism, adhesion, and migration associated with c-Rel activation. In contrast, REL amplification did not correlate with c-Rel nuclear expression and patient survival, likely due to co-amplification of genes that negatively regulate NF-kappaB activation. These insights into the expression, prognostic impact, regulation and function of c-Rel as well as its crosstalk with the p53 pathway underscore the importance of c-Rel and have significant therapeutic implications.
Details
- Database :
- OAIster
- Journal :
- Oncotarget; 23157; 23180; 1949-2553; 27; 6; ~Oncotarget~23157~23180~~~1949-2553~27~6~~
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.on1284034736
- Document Type :
- Electronic Resource