Expression and function of the TL1A/DR3 axis in chronic lymphocytic leukemia

Cavallini, Chiara; Lovato, Ornella; Bertolaso, Anna; Zoratti, Elisa; Malpeli, Giorgio; Mimiola, Elda; Tinelli, Martina; Aprili, Fiorenza; Tecchio, Cristina; Perbellini, Omar; Scarpa, Aldo; Zamò, Alberto; Cassatella, Marco A.; Pizzolo, Giovanni; Scupoli, Maria Teresa

doi:10.18632/oncotarget.5201

Cited by 12 publications

(8 citation statements)

References 52 publications

(68 reference statements)

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“…Our lab extended these findings and showed that in the absence of cIAPs DR3 stimulation allowed full‐blown apoptosis induction in the leukemia cell lines TF‐1 and Ku812F . Notably, DR3 expression has also been reported in B cells isolated from patients with chronic lymphocytic leukemia . Combinatorial treatments with SMAC mimetics and DR3 agonists could therefore hold therapeutic potential in some cancer entities.…”

Section: Molecular Mechanisms Of Dr3 Signalingsupporting

confidence: 58%

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Multifaceted death receptor 3 signaling—promoting survival and triggering death

Bittner

Ehrenschwender

2017

FEBS Letters

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Death Receptor 3 (DR3) and its cognate ligand TL1A belong to the tumor necrosis factor superfamily (TNFSF). This sophisticated network of receptor-ligand systems controls innumerable biological processes. For many (if not all) TNFSF ligands and receptors, a role in conditions such as inflammation, tissue development, proliferation, and cell death has been firmly established. However, relatively little is known about DR3 and TL1A. Here, we review novel aspects of DR3 signaling and DR3-associated signaling pathways before summarizing the function of DR3 in the immune system. The emerging role of DR3 in disease will be addressed before we finally critically discuss the potential therapeutic exploitation of this receptor-ligand pair.

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Section: Molecular Mechanisms Of Dr3 Signalingsupporting

confidence: 58%

“…Notably, DR3 expression has also been reported in B cells isolated from patients with chronic lymphocytic leukemia [39]. Combinatorial treatments with SMAC mimetics and DR3 agonists could therefore hold therapeutic potential in some cancer entities.…”

Section: Cell Death Pathways Triggered By Dr3mentioning

confidence: 98%

Multifaceted death receptor 3 signaling—promoting survival and triggering death

Bittner

Ehrenschwender

2017

FEBS Letters

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“…The receptor stimulates sNF-kappa B activity and regulates cell apoptosis. TNFRSF25 was differentially expressed activating CLL cells and predominantly detecting in those with early clinical stage disease (37), and probably alters the balance between cell proliferation and death, in uencing CLL physiopathology and results in the clinic.…”

Section: Disscusionmentioning

confidence: 99%

Super-Enhancer Associated Nine-gene Prognostic Score Model for Prediction of Survival in Chronic Lymphoic Leukemia Patients

Liang

Yang

et al. 2021

Preprint

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BackgroundChronic lymphocytic leukemia (CLL) is a group of highly heterogeneous mature B cell malignancy with various disease courses and diagnoses. Super-enhancer(SE) is a novel concept drew in recent years which is a cluster of enhancers involved in cell differentiation and tumorigenesis ,and is one of the promising therapeutic targets for cancer therapy. Although there is a multitude of prognostic markers in CLL, insights into the role of super-enhancer(SE)-related risk indicators are still lacking.MethodsThe CLL-related super-enhancers in training database were processed by Lasso penalized Cox regression analysis to screen a nine-gene prognostic model. And the associations between all of the individual markers and OS of CLL were assessed by Cox regression analysis. Besides, in order to understand the connection between individual genes and selected disease characteristics, like IGHV mutation status, FISH abnormality, and ZAP70 expression level, we performed correlation analysis.ResultsA nine-gene prognostic model was screened, including TCF7, VEGFA, MNT, GMIP, SLAMF1, TNFRSF25, GRWD1, SLC6AC, and LAG3. A SE-related risk score was further constructed and the robust predictive performance with 5-year survival and time-to-treatment (TTT) area under the curve(AUC): 0.997 and 1.000 in the training database and 0.628 and 0.673 in the testing database, respectively. Besides, a high correlation was found between the risk score and known prognostic markers of CLL, including the mutational status of immunoglobulin variable region loci (IGHV), chromosomal abnormalities, and ZAP70 expression. Meantime, we noticed that the expression of TCF7, GMIP, SLAMF1, TNFRSF25, and LAG3 in CLL were different from healthy donors(P<0.01), moreover, the risk score and LAG3 level of matched pairs before and after treatment samples varied significantly, although these results were not completely consistent in different datasets. ConclusionTherefore, the SE-associated nine-gene prognostic model developed here may be used to predict the prognosis and assist in the risk stratification of CLL patients in the future.

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“…TNF-like ligand 1A (TL1A; also known as TNFSF15 or VEGI), is a unique cytokine produced by endothelial cells, T cells, macrophages, monocytes and dendritic cells, which inhibits proliferation and angiogenesis of endothelial cells 5,67.…”

Section: Introductionmentioning

confidence: 99%

<p>TNF-like ligand 1A is associated with progression and prognosis of human gastric cancer</p>

Gao

Wang

Xiao

et al. 2019

OTT

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PurposeThis study aimed to investigate the function of TNF-like ligand 1A (TL1A) in the tumorigenesis and progression of gastric cancer (GC).MethodsRNA-seq gene expression and clinical information for GC patients were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) between GC tissue samples and normal controls were screened with the edgeR package. Identification of gene co-expression and functional enrichment analyses were performed with Pearson’s correlation analysis and gene set enrichment analysis (GSEA), respectively. Lastly, survival analysis was performed using the Kaplan-Meier method with the log rank test.ResultsTL1A expression in GC tissue samples were significantly higher than that in normal controls (LogFC=1.07 and P=8.90E-07). Moreover, 215 genes, co-expressed with TL1A, and 21 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were obtained. Next, the miRNA-lncRNA/mRNA network, comprising 7 miRNAs, 27 lncRNAs, and 21 mRNAs, was constructed based on key genes from intersections between co-expression analysis and GSEA. In addition, survival analysis results demonstrated that TL1A (P=2.6e−07) was significantly associated with the overall survival (OS) of GC patients.ConclusionTL1A was involved in the tumorigenesis and progression of GC, and was significantly associated with the OS of GC patients.

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Expression and function of the TL1A/DR3 axis in chronic lymphocytic leukemia

Cited by 12 publications

References 52 publications

Multifaceted death receptor 3 signaling—promoting survival and triggering death

Multifaceted death receptor 3 signaling—promoting survival and triggering death

Super-Enhancer Associated Nine-gene Prognostic Score Model for Prediction of Survival in Chronic Lymphoic Leukemia Patients

<p>TNF-like ligand 1A is associated with progression and prognosis of human gastric cancer</p>

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