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      Deregulation of CircANXA2, Circ0075001, and CircFBXW7 Gene Expressions and Their Predictive Value in Egyptian Acute Myeloid Leukemia Patients

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          Abstract

          Background

          Acute myeloid leukemia (AML) is of heterogeneous pathogenesis and caused by alterations of multiple genes. CircRNAs act as oncogenes or tumor suppressors in numerous tumors and could be novel diagnostic and prognostic biomarkers. Few studies had incorporated circRNAs in AML.

          Aim of the Work

          Assessment of circANXA2, circ0075001, and circFBXW7 gene expressions in AML patients. Evaluation of their relations with clinical, cytogenetic, and overall survival outcome to emphasize their diagnostic role and prognostic impact.

          Methods

          This study was carried out on 120 subjects (66 AML patients and 54 controls). All subjects were subjected to gene expressions assay for circANXA2, circ0075001, circFBXW7 by quantitative real-time polymerase chain reaction.

          Results

          Prominent overexpression of circANAX2 and circ0075001 in patients than control (P < 0.001), whereas circFBXW7 was markedly downregulated in patients than in control (P < 0.001). Moreover, circANXA2 with AUC 0.824, P <0.001, had a sensitivity of 74.24%, specificity 88.89% whereas circ0075001 with AUC 0.855, P < 0.001, had the highest sensitivity of 83.33% and specificity 79.63%, and circFBXW7 with AUC 0.826, P < 0.001, had a sensitivity of 75.76% and specificity 74.07% in the distinction of AML patients from controls. Additionally, we find out that high expression of circANXA2 and circ0075001 correlated significantly with splenomegaly, hepatomegaly, less differentiated FAB subtypes (M5, M7), short overall survival, and had an adverse cytogenetic pattern.

          Conclusion

          CircANXA2, circ0075001, and circFBXW7 gene expressions could serve as potential diagnostic biomarkers for AML disease. Moreover, CircANXA2 and circ0075001 exert poor prognostic effects on AML patients.

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          Most cited references44

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          Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel.

          The first edition of the European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML) in adults, published in 2010, has found broad acceptance by physicians and investigators caring for patients with AML. Recent advances, for example, in the discovery of the genomic landscape of the disease, in the development of assays for genetic testing and for detecting minimal residual disease (MRD), as well as in the development of novel antileukemic agents, prompted an international panel to provide updated evidence- and expert opinion-based recommendations. The recommendations include a revised version of the ELN genetic categories, a proposal for a response category based on MRD status, and criteria for progressive disease.
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            Acute Myeloid Leukemia.

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              The Biogenesis, Functions, and Challenges of Circular RNAs

              Covalently closed circular RNAs (circRNAs) are produced by precursor mRNA back-splicing of exons of thousands of genes in eukaryotes. circRNAs are generally expressed at low levels and often exhibit cell-type-specific and tissue-specific patterns. Recent studies have shown that their biogenesis requires spliceosomal machinery and can be modulated by both cis complementary sequences and protein factors. The functions of most circRNAs remain largely unexplored, but known functions include sequestration of microRNAs or proteins, modulation of transcription and interference with splicing, and even translation to produce polypeptides. However, challenges exist at multiple levels to understanding of the regulation of circRNAs because of their circular conformation and sequence overlap with linear mRNA counterparts. In this review, we survey the recent progress on circRNA biogenesis and function and discuss technical obstacles in circRNA studies.
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                Author and article information

                Journal
                Appl Clin Genet
                Appl Clin Genet
                tacg
                The Application of Clinical Genetics
                Dove
                1178-704X
                16 July 2022
                2022
                : 15
                : 69-85
                Affiliations
                [1 ]Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Menoufia University , Shebin El-Kom, 32511, Egypt
                [2 ]Clinical Pathology Department, Faculty of Medicine, Menoufia University , Shebin El-Kom, 32511, Egypt
                [3 ]Hematology Unit, Department of Internal Medicine, Faculty of Medicine, Menoufia University , Shebin El-Kom, 32511, Egypt
                [4 ]Clinical Oncology and Nuclear Medicine Department, Faculty of Medicine, Menoufia University , Shebin El-Kom, 32511, Egypt
                Author notes
                Correspondence: Safaa I Tayel, Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Menoufia University , Shebin El-Kom, Menoufia, Egypt, Email drsafaa_tayel@yahoo.com
                Author information
                http://orcid.org/0000-0002-6528-0256
                http://orcid.org/0000-0001-9927-7277
                http://orcid.org/0000-0002-0061-6652
                Article
                365613
                10.2147/TACG.S365613
                9300747
                35874179
                8e5207fe-edf0-4459-8d34-8e7772959b1b
                © 2022 Tayel et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 09 March 2022
                : 17 June 2022
                Page count
                Figures: 2, Tables: 18, References: 48, Pages: 17
                Funding
                Funded by: funding;
                There is no funding to report.
                Categories
                Original Research

                acute myeloid leukemia,circrnas,circanxa2,circ0075001,circfbxw7

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