The relationship of REL proto-oncogene to pathobiology and chemoresistance in follicular and transformed follicular lymphoma

Hu, Xiaozhou; Baytak, Esra; Li, Jinnan; Akman, Burcu; Okay, Kaan; Hu, Genfu; Scuto, Anna; Zhang, Wenyan; Küçük, Can

doi:10.1016/j.leukres.2017.01.001

Cited by 6 publications

(10 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, GSEA analysis found an enrichment towards the “dead and high TNFRSF14 phenotype” of the NF-kB pathway. Of note, the NF-kB pathway is related to the pathobiology and chemoresistance in FL and tFL 39 . It has been reported that deletions of 1p36 and TNFRSF14 mutations are associated with worse prognosis of FL, but in that publication the authors did not analyze the protein expression of TNFRSF14 40 and, unfortunately, in our study we have not analyzed the mutational status.…”

Section: Discussionmentioning

confidence: 80%

High TNFRSF14 and low BTLA are associated with poor prognosis in Follicular Lymphoma and in Diffuse Large B-cell Lymphoma transformation

Carreras¹,

López‐Guillermo²,

Kikuti³

et al. 2019

JCEH

View full text Add to dashboard Cite

The microenvironment influences the behavior of follicular lymphoma (FL) but the specific roles of the immunomodulatory BTLA and TNFRSF14 (HVEM) are unknown. Therefore, we examined their immunohistochemical expression in the intrafollicular, interfollicular and total histological compartments in 106 FL cases (57M/49F; median age 57-years), and in nine relapsed-FL with transformation to DLBCL (tFL). BTLA expression pattern was of follicular T-helper cells (TFH) in the intrafollicular and of T-cells in the interfollicular compartments. The mantle zones were BTLA+ in 35.6% of the cases with similar distribution of IgD. TNFRSF14 expression pattern was of neoplastic B lymphocytes (centroblasts) and “tingible body macrophages”. At diagnosis, the averages of total BTLA and TNFRSF14-positive cells were 19.2%±12.4STD (range, 0.6%-58.2%) and 46.7 cells/HPF (1-286.5), respectively. No differences were seen between low-grade vs. high-grade FL but tFL was characterized by low BTLA and high TNFRSF14 expression. High BTLA correlated with good overall survival (OS) (total-BTLA, Hazard Risk=0.479, P =0.022) and with high PD-1 and FOXP3+Tregs. High TNFRSF14 correlated with poor OS and progression-free survival (PFS) (total-TNFRSF14, HR=3.9 and 3.2, respectively, P<0.0001), with unfavorable clinical variables and higher risk of transformation (OR=5.3). Multivariate analysis including BTLA, TNFRSF14 and FLIPI showed that TNFRSF14 and FLIPI maintained prognostic value for OS and TNFRSF14 for PFS. In the GSE16131 FL series, high TNFRSF14 gene expression correlated with worse prognosis and GSEA showed that NFkB pathway was associated with the “High-TNFRSF14/dead-phenotype”. In conclusion, the BTLA-TNFRSF14 immune modulation pathway seems to play a role in the pathobiology and prognosis of FL.

show abstract

Section: Discussionmentioning

confidence: 80%

High TNFRSF14 and low BTLA are associated with poor prognosis in Follicular Lymphoma and in Diffuse Large B-cell Lymphoma transformation

Carreras¹,

López‐Guillermo²,

Kikuti³

et al. 2019

JCEH

View full text Add to dashboard Cite

show abstract

“…For example, RelB is involved in the regulation of cell cycle and can predict good prognosis in glioma [ 19 ]. Similarly, high REL levels have been shown to predict response to immunochemotherapy in follicular lymphoma [ 20 ]. It is therefore likely that NF- κ B family subunits may influence the tumorigenesis and progression of HCC.…”

Section: Discussionmentioning

confidence: 99%

Mining Database for the Expression and Clinical Significance of NF-κB Family in Hepatocellular Carcinoma

Zhou

Zhe-cheng

et al. 2020

Journal of Oncology

View full text Add to dashboard Cite

Background. Hepatocellular carcinoma (HCC) is one of the deadliest diseases affecting humans. Its incidence has been increasing over the last decade. It is characterized by poor prognosis as well as lack of therapeutic regimens for patients in the advanced stages. It is therefore important to develop effective biomarkers for diagnosis, prognosis, and immunotherapy of HCC. Research suggests that the NF-κB family plays vital roles in immune response, inflammation, tumorigenesis, and the progress of malignancy in various cancers. However, its role in HCC remains unidentified. Methodology. The expression and clinical significance of the NF-κB family in HCC were analyzed using several bioinformatics tools including UALCAN, The Human Protein Atlas, GEPIA, GSCALite, David, GeneMANIA, and TIMER. Results. The mRNA expression levels of RelA, RelB, NF-κB1, and NF-κB2 were significantly elevated in HCC. The mRNA levels of RelB and NF-κB2 were significantly upregulated in HCC tissues compared to normal liver tissues in subgroup analyses based on patient’s race, gender, age, weight, tumor grade, cancer stage, and nodal metastasis status. Moreover, HCC patients with elevated levels of RelB and NF-κB2 had a worse overall survival and disease-free survival. Methylation downregulated the expressions of RelA, RelB, and NF-κB1 in HCC. NF-κB family was also significantly involved in various hallmark cancer-related pathways such as the apoptosis, EMT, RTK, and cell cycle pathways. Similarly, the expression of RelB and NF-κB2 was positively correlated with the abundance of immune cells and the expression of immune biomarkers. Several kinase and miRNA targets of RelB and NF-κB2 were also identified. Conclusion. RelB and NF-κB2 are potential biomarkers for the diagnosis, prognosis, and immunotherapy of HCC.

show abstract

“…REL is one of the protooncogenes identified to reside on the frequently amplified 2p16.1-p15 locus in FL and tFL cases based on this study. Recently, Hu et al showed that FL cases with high REL expression levels may be associated with chemotherapy resistance due to activation of DNA damage-induced repair and cell cycle arrest pathways; however, future studies are needed to investigate whether REL is a predictive biomarker of chemotherapy in FL and/or tFL cases (Hu et al, 2017). Another recent study systematically analyzed genes in the frequently amplified 2p16.1-p15 locus by integrating an SNP array and gene expression profiling data of previously published reports on FL and tFL cases to address whether there are genes other than REL that may act as protooncogenes during transformation to tFL (Kurşun and Küçük, 2019).…”

Section: Chemotherapy Resistance-associated Genetic Aberrations In B mentioning

confidence: 99%

Genetic alterations in B cell lymphoma subtypes as potential biomarkers for non-invasive diagnosis, prognosis, therapy, and disease monitoring

Sönmez

Küçük

2020

Turk J Biol

View full text Add to dashboard Cite

Neoplastic transformation of germinal center B (GCB) cells may give rise to a variety of different B cell lymphoma subtypes, most of which show substantial heterogeneity in terms of genetic alterations and clinical features. The mutations observed in cancerrelated genes in GCB cells are related to abnormalities in the immunogenetic mechanisms associated with germinal center reaction. Recent studies have rapidly identified genomic alterations in B cell lymphomas that may be useful for better subclassification, noninvasive diagnosis, and prediction of response to therapy. The WHO recognizes different lymphoma subsets classified within 2 major categories of B cell lymphoma: Hodgkin's lymphoma (HL) and B cell non-Hodgkin's lymphoma (NHL), each with distinct genetic aberrations, including chromosomal translocations, copy number abnormalities, or point mutations. Next-generation sequencing-based technologies have allowed cancer researchers to identify somatic mutations and gene expression signatures at a rapid pace so that novel diagnostic or prognostic biomarkers, as well as therapeutic targets, can be discovered much faster than before. Indeed, deep sequencing studies have recently revealed that lymphoma-specific somatic mutations may be detected in cell-free circulating DNA obtained from the peripheral blood of B cell lymphoma patients, suggesting the possibility of minimally invasive diagnosis, monitoring, and predicting response to therapy of B cell lymphoma patients. In this study, the current status of the recurrent genetic aberrations observed during diagnosis and/ or relapse in HL and the major subtypes of B cell NHL (i.e. diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma, and Burkitt lymphoma) are discussed to shed light on their potential use as noninvasive diagnostic or prognostic biomarkers and to reveal their role in lymphomagenesis as a target in therapy for newly diagnosed and chemotherapy-resistant cases.

show abstract

The relationship of REL proto-oncogene to pathobiology and chemoresistance in follicular and transformed follicular lymphoma

Cited by 6 publications

References 53 publications

High TNFRSF14 and low BTLA are associated with poor prognosis in Follicular Lymphoma and in Diffuse Large B-cell Lymphoma transformation

High TNFRSF14 and low BTLA are associated with poor prognosis in Follicular Lymphoma and in Diffuse Large B-cell Lymphoma transformation

Mining Database for the Expression and Clinical Significance of NF-κB Family in Hepatocellular Carcinoma

Genetic alterations in B cell lymphoma subtypes as potential biomarkers for non-invasive diagnosis, prognosis, therapy, and disease monitoring

Contact Info

Product

Resources

About