Expression and prognostic value of FAS receptor/FAS ligand and TrailR1/TrailR2 in acute myeloid leukemia

Pordzik, Sandra; Petrovici, Karin; Schmid, Christoph; Kroell, Tanja; Schweiger, C.; Köhne, Claus‐Henning; Schmetzer, Helga

doi:10.1179/102453311x13127324303353

Cited by 9 publications

(7 citation statements)

References 28 publications

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“…Lower expression of these molecules, which are involved in the commencement of the apoptotic pathway, aids cancerous cells in avoiding apoptosis. In line with our results, Prodzik et al, using flowcytometry, reported a significantly lower expression of FAS and DR4 in AML patients compared to controls ( 3 ). As the mentioned study evaluated the protein expression, it also confirms that gene expression levels of FAS and DR4 show a good correlation with the protein expression levels.…”

Section: Discussionsupporting

confidence: 93%

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Expression of DR4, DR5, FAS, Caspase-8 and, DDIAS Genes in AML Patients

Naghinezhad,

Alenabi,

Ayatollahi

et al. 2023

MJIRI

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Background Acute myeloid leukemia (AML) is the most common acute leukemia in adults and accompanies a worse survival. In this study, gene expression levels of 5 key players of apoptosis, including DR4, DR5, FAS, caspase 8, and DNA damage-induced apoptosis suppressor (DDIAS), have been evaluated in AML patients compared with controls, aiming to evaluate their possible role and prognostic impact. Methods This cross-sectional study was performed in the Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences. A total of 30 newly diagnosed AML cases as well as 30 healthy controls enrolled in the study. Real-time polymerase chain reaction was used to evaluate the expressions of DR4, DR5, FAS, DDIAS, and caspase 8 genes in cases and controls. Other necessary data, including cytogenetic findings, mutations, French-American-British (FAB) classification, and survival, were retrieved from hospital records and by direct contact with patients. Statistical analysis was done by SPSS software. When appropriate, the Mann-Whitney U, Pearson's correlation, and the t tests were utilized. Overall survival (OS) was estimated using the Kaplan-Meier method. Results The expression of all evaluated genes, including DDIAS (0.89 ± 0.20), DR4 (0.67 ± 0.24), DR5 (0.72 ± 0.24), FAS (0.70 ± 0.25), and Caspase 8 (0.77 ± 0.20) were significantly decreased in AML patients compared with the controls ( P < 0.001). Patients with the t (16;16) or inv (16) expressed significantly higher amounts of the FAS gene and those with FLT3 mutation exhibited lower expression of caspase 8. Expression of the evaluated genes showed no significant effect on survival. Conclusion The expression of DR4, DR5, FAS, and caspase 8 seems to be decreased in AML. Lower expression of these molecules may aid AML cells in avoiding apoptosis because they are involved in the initiation of apoptosis, making them potential targets for treatment.

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Section: Discussionsupporting

confidence: 93%

“…A better understanding of the genetic and molecular basis of AML may lead to improve treatment outcomes for patients. Evasion of programmed cell death (apoptosis) is a key step in cancer pathogenesis ( 3 ). There are 2 main apoptotic pathways: extrinsic and intrinsic.…”

Section: Introductionmentioning

confidence: 99%

Expression of DR4, DR5, FAS, Caspase-8 and, DDIAS Genes in AML Patients

Naghinezhad,

Alenabi,

Ayatollahi

et al. 2023

MJIRI

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“…Likewise, most immunohistochemical studies performed so far to evaluate TRAIL receptor expression in primary tumour tissues are poorly informative due to a lack of specific evaluation of membrane‐bound expression levels of these receptors. Nonetheless, heterogeneous expression levels of TRAIL receptors have been found in a large variety of tumours (Strater et al ., ; Min et al ., ; McCarthy et al ., ; van Geelen et al ., ; Kuijlen et al ., ; Cooper et al ., ; Granci et al ., ; Ganten et al ., ; Leithner et al ., ; Macher‐Goeppinger et al ., ; Pordzik et al ., ). However, their expression level is probably overestimated by the fact that most of these studies revealed mainly cytoplasmic expression.…”

Section: Study Design and Administration Of Trail And Derivatives: Lementioning

confidence: 99%

Death receptors as targets in cancer

Micheau

Shirley

Dufour

2013

British J Pharmacology

175

167

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Anti-tumour therapies based on the use pro-apoptotic receptor agonists, including TNF-related apoptosis-inducing ligand (TRAIL) or monoclonal antibodies targeting TRAIL-R1 or TRAIL-R2, have been disappointing so far, despite clear evidence of clinical activity and lack of adverse events for the vast majority of these compounds, whether combined or not with conventional or targeted anti-cancer therapies. This brief review aims at discussing the possible reasons for the lack of apparent success of these therapeutic approaches and at providing hints in order to rationally design optimal protocols based on our current understanding of TRAIL signalling regulation or resistance for future clinical trials. LINKED ARTICLESThis article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx

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“…The out of control regulation of apoptosis could make a contribution to the pathogenesis of malignancies, such as ovarian cancer, breast cancer and neuroblastoma ( 5 – 7 ). Among haematological cancers, Fas-mediated apoptosis was presented in multiple myeloma, Burkitt's lymphoma and acute myeloid leukemia (AML) ( 8 – 11 ).…”

Section: Introductionmentioning

confidence: 99%

Fas-670A>G polymorphism is not associated with an increased risk of acute myeloid leukemia development

Huang

Deng

et al. 2015

Biomedical Reports

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The association between the increased risk of acute myeloid leukemia (AML) and Fas promoter polymorphisms has been reported previously; however, the results are inconclusive. The present study performed one case-control study to investigate the association, and a total of 98 AML patients and 2,014 healthy controls were genotyped. The data showed that the distribution of Fas-670AA, GA and GG genotypes among the AML patients were not significantly different from those of the healthy controls, all P>0.05. Following this a sub-study was conducted to analyze individuals who neither smoked nor drank. The results demonstrated that there was still no significant association between the Fas-670 polymorphism and risk of AML development, all P>0.05. Furthermore, in order to address a more accurate estimation of the association, a meta-analysis was conducted. Data were systematically collected from the Pubmed, EMBASE and the Wanfang Library. A total of 3 studies were included in this meta-analysis, which contained 1,144 AML cases and 3,806 controls. No significant association was detected between the Fas-670A>G polymorphism and AML risk [GA+GG vs. AA: odds ratio (OR) 0.93; 95% confidence interval (CI), 0.79–1.09; GG vs. AA: OR, 1.01; 95% CI, 0.82–1.24; GA vs. AA: OR, 1.12; 95% CI, 0.94–1.32; GG vs. AA+GA: OR, 0.94; 95% CI, 0.79–1.12; G vs. A: OR, 1.01; 95% CI, 0.91–1.12; all P>0.05). The analysis clearly indicated that there was no significant connection between the Fas-670A>G polymorphism and the increased risk of AML.

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Expression and prognostic value of FAS receptor/FAS ligand and TrailR1/TrailR2 in acute myeloid leukemia

Cited by 9 publications

References 28 publications

Expression of DR4, DR5, FAS, Caspase-8 and, DDIAS Genes in AML Patients

Expression of DR4, DR5, FAS, Caspase-8 and, DDIAS Genes in AML Patients

Death receptors as targets in cancer

Fas-670A>G polymorphism is not associated with an increased risk of acute myeloid leukemia development

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