ArticleOncotarget2015
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.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- LMP1 enhances aerobic glycolysis in natural killer/T cell lymphoma.Cell death & disease · 2024Article
- Altered pathways and targeted therapy in double hit lymphoma.Journal of hematology & oncology · 2022Review
- Article
- c-Rel Is the Pivotal NF-κB Subunit in Germinal Center Diffuse Large B-Cell Lymphoma: A LYSA Study.Frontiers in oncology · 2021Article
- Regulation of B-cell function by NF-kappaB c-Rel in health and disease.Cellular and molecular life sciences : CMLS · 2020Review
- Constitutive expression of c-REL in uveal melanoma patients: correlation with clinicopathological parameters and patient outcome.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Article
- c-Rel gain in B cells drives germinal center reactions and autoantibody production.The Journal of clinical investigation · 2020Article
- Comparative pathologic analysis of mediastinal B-cell lymphomas: selective expression of p63 but no GATA3 optimally differentiates primary mediastinal large B-cell lymphoma from classic Hodgkin lymphoma.Diagnostic pathology · 2019Article
- Genetic alterations and their clinical implications in DLBCL.Nature reviews. Clinical oncology · 2019Review
- A Hydroquinone-Based Derivative Elicits Apoptosis and Autophagy via Activating a ROS-Dependent Unfolded Protein Response in Human Glioblastoma.International journal of molecular sciences · 2019Article
- Mechanisms of apoptosis modulation by curcumin: Implications for cancer therapy.Journal of cellular physiology · 2019Review
- The Unsolved Puzzle of c-Rel in B Cell Lymphoma.Cancers · 2019Review
- Identification of canonical NFκB (C-NFκB) pathway in uveal melanoma and their relation with patient outcome.Clinical & experimental metastasis · 2019Article
- Tumor Microenvironment in Diffuse Large B-Cell Lymphoma: Role and Prognosis.Analytical cellular pathology (Amsterdam) · 2019Review
- AKT Hyperactivation and the Potential of AKT-Targeted Therapy in Diffuse Large B-Cell Lymphoma.The American journal of pathology · 2017Article
- Comparative gene-expression profiling of the large cell variant of gastrointestinal marginal-zone B-cell lymphoma.Scientific reports · 2017Article
- NF-κB p50 activation associated with immune dysregulation confers poorer survival for diffuse large B-cell lymphoma patients with wild-type p53.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2017Article
- NF-κB signaling pathway and its potential as a target for therapy in lymphoid neoplasms.Blood reviews · 2017Review
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Corrections and comments
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Authors and funding
29 authors at 20 institutions in 9 countries.
Funding
Abstract
Dysregulated NF-κB signaling is critical for lymphomagenesis. The regulation, function, and clinical relevance of c-Rel/NF-κB 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-κB 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-κB 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.
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