Aberrant DNA methylation of PTPRG as one possible mechanism of its under‐expression in CML patients in the State of Qatar
Abstract Background Several studies showed that aberrant DNA methylation is involved in leukemia and cancer pathogenesis. Protein tyrosine phosphatase receptor gamma (PTPRG) expression is a natural inhibitory mechanism that is downregulated in chronic myeloid leukemia (CML) disease. The mechanism be...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-10-01
|
| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.1319 |
| _version_ | 1827198121063481344 |
|---|---|
| author | Mohamed A. Ismail Muthanna Samara Ali Al Sayab Mohamed Alsharshani Mohamed A. Yassin Govindarajulu Varadharaj Marzia Vezzalini Luisa Tomasello Maria Monne Hisham Morsi M. Walid Qoronfleh Hatem Zayed Richard Cook Claudio Sorio Helmout Modjtahedi Nader I. Al‐Dewik |
| author_facet | Mohamed A. Ismail Muthanna Samara Ali Al Sayab Mohamed Alsharshani Mohamed A. Yassin Govindarajulu Varadharaj Marzia Vezzalini Luisa Tomasello Maria Monne Hisham Morsi M. Walid Qoronfleh Hatem Zayed Richard Cook Claudio Sorio Helmout Modjtahedi Nader I. Al‐Dewik |
| author_sort | Mohamed A. Ismail |
| collection | DOAJ |
| description | Abstract Background Several studies showed that aberrant DNA methylation is involved in leukemia and cancer pathogenesis. Protein tyrosine phosphatase receptor gamma (PTPRG) expression is a natural inhibitory mechanism that is downregulated in chronic myeloid leukemia (CML) disease. The mechanism behind its downregulation has not been fully elucidated yet. Aim This study aimed to investigate the CpG methylation status at the PTPRG locus in CML patients. Methods Peripheral blood samples from CML patients at time of diagnosis [no tyrosine kinase inhibitors (TKIs)] (n = 13), failure to (TKIs) treatment (n = 13) and healthy controls (n = 6) were collected. DNA was extracted and treated with bisulfite treatment, followed by PCR, sequencing of 25 CpG sites in the promoter region and 26 CpG sites in intron‐1 region of PTPRG. The bisulfite sequencing technique was employed as a high‐resolution method. Results CML groups (new diagnosed and failed treatment) showed significantly higher methylation levels in the promoter and intron‐1 regions of PTPRG compared to the healthy group. There were also significant differences in methylation levels of CpG sites in the promoter and intron‐1 regions amongst the groups. Conclusion Aberrant methylation of PTPRG is potentially one of the possible mechanisms of PTPRG downregulation detected in CML. |
| first_indexed | 2024-03-07T23:15:17Z |
| format | Article |
| id | doaj.art-a3a4fc0e01ad4936bd8a4d7c9f95ad23 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2025-03-21T10:11:59Z |
| publishDate | 2020-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-a3a4fc0e01ad4936bd8a4d7c9f95ad232024-07-04T06:31:51ZengWileyMolecular Genetics & Genomic Medicine2324-92692020-10-01810n/an/a10.1002/mgg3.1319Aberrant DNA methylation of PTPRG as one possible mechanism of its under‐expression in CML patients in the State of QatarMohamed A. Ismail0Muthanna Samara1Ali Al Sayab2Mohamed Alsharshani3Mohamed A. Yassin4Govindarajulu Varadharaj5Marzia Vezzalini6Luisa Tomasello7Maria Monne8Hisham Morsi9M. Walid Qoronfleh10Hatem Zayed11Richard Cook12Claudio Sorio13Helmout Modjtahedi14Nader I. Al‐Dewik15School of Life Science, Pharmacy and Chemistry Faculty of Science, Engineering & ComputingFaculty of Science, Engineering & Computing Kingston University London Kingston‐Upon‐Thames UKDepartment of Psychology Kingston University London Kingston upon Thames, London UKInterim Translational Research Institute (iTRI)Hamad Medical Corporation (HMC) Doha QatarDiagnostic Genetics Division (DGD) Department of Laboratory Medicine and Pathology (DLMP) Hamad Medical Corporation (HMC) Doha QatarDepartment of Medical Oncology National Centre for Cancer Care and ResearchHamad Medical Corporation (HMC) Doha QatarGenetrics Inc Dubai United Arab EmiratesGeneral Pathology Division Department of Medicine University of Verona Verona ItalyWexner Medical Center Biomedical Research Tower The Ohio State University Columbus OH USACentro di Diagnostica Biomolecolare e Citogenetica Emato‐Oncologica San Francesco” Hospital Nuoro ItalyQuality of Life unit National Center for Cancer Care and Research, (NCCCR) Hamad Medical Corporation (HMC) Doha QatarWorld Innovation Summit for Healthcare (WISH) Qatar Foundation Doha QatarDepartment of Biomedical Sciences Biomedical Research CenterCollege of Health SciencesQU HealthQatar University Doha QatarSchool of Life Science, Pharmacy and Chemistry Faculty of Science, Engineering & ComputingFaculty of Science, Engineering & Computing Kingston University London Kingston‐Upon‐Thames UKGeneral Pathology Division Department of Medicine University of Verona Verona ItalySchool of Life Science, Pharmacy and Chemistry Faculty of Science, Engineering & ComputingFaculty of Science, Engineering & Computing Kingston University London Kingston‐Upon‐Thames UKSchool of Life Science, Pharmacy and Chemistry Faculty of Science, Engineering & ComputingFaculty of Science, Engineering & Computing Kingston University London Kingston‐Upon‐Thames UKAbstract Background Several studies showed that aberrant DNA methylation is involved in leukemia and cancer pathogenesis. Protein tyrosine phosphatase receptor gamma (PTPRG) expression is a natural inhibitory mechanism that is downregulated in chronic myeloid leukemia (CML) disease. The mechanism behind its downregulation has not been fully elucidated yet. Aim This study aimed to investigate the CpG methylation status at the PTPRG locus in CML patients. Methods Peripheral blood samples from CML patients at time of diagnosis [no tyrosine kinase inhibitors (TKIs)] (n = 13), failure to (TKIs) treatment (n = 13) and healthy controls (n = 6) were collected. DNA was extracted and treated with bisulfite treatment, followed by PCR, sequencing of 25 CpG sites in the promoter region and 26 CpG sites in intron‐1 region of PTPRG. The bisulfite sequencing technique was employed as a high‐resolution method. Results CML groups (new diagnosed and failed treatment) showed significantly higher methylation levels in the promoter and intron‐1 regions of PTPRG compared to the healthy group. There were also significant differences in methylation levels of CpG sites in the promoter and intron‐1 regions amongst the groups. Conclusion Aberrant methylation of PTPRG is potentially one of the possible mechanisms of PTPRG downregulation detected in CML.https://doi.org/10.1002/mgg3.1319aberrant DNAcancerCMLepigeneticsmethylationPTPRG |
| spellingShingle | Mohamed A. Ismail Muthanna Samara Ali Al Sayab Mohamed Alsharshani Mohamed A. Yassin Govindarajulu Varadharaj Marzia Vezzalini Luisa Tomasello Maria Monne Hisham Morsi M. Walid Qoronfleh Hatem Zayed Richard Cook Claudio Sorio Helmout Modjtahedi Nader I. Al‐Dewik Aberrant DNA methylation of PTPRG as one possible mechanism of its under‐expression in CML patients in the State of Qatar Molecular Genetics & Genomic Medicine aberrant DNA cancer CML epigenetics methylation PTPRG |
| title | Aberrant DNA methylation of PTPRG as one possible mechanism of its under‐expression in CML patients in the State of Qatar |
| title_full | Aberrant DNA methylation of PTPRG as one possible mechanism of its under‐expression in CML patients in the State of Qatar |
| title_fullStr | Aberrant DNA methylation of PTPRG as one possible mechanism of its under‐expression in CML patients in the State of Qatar |
| title_full_unstemmed | Aberrant DNA methylation of PTPRG as one possible mechanism of its under‐expression in CML patients in the State of Qatar |
| title_short | Aberrant DNA methylation of PTPRG as one possible mechanism of its under‐expression in CML patients in the State of Qatar |
| title_sort | aberrant dna methylation of ptprg as one possible mechanism of its under expression in cml patients in the state of qatar |
| topic | aberrant DNA cancer CML epigenetics methylation PTPRG |
| url | https://doi.org/10.1002/mgg3.1319 |
| work_keys_str_mv | AT mohamedaismail aberrantdnamethylationofptprgasonepossiblemechanismofitsunderexpressionincmlpatientsinthestateofqatar AT muthannasamara aberrantdnamethylationofptprgasonepossiblemechanismofitsunderexpressionincmlpatientsinthestateofqatar AT alialsayab aberrantdnamethylationofptprgasonepossiblemechanismofitsunderexpressionincmlpatientsinthestateofqatar AT mohamedalsharshani aberrantdnamethylationofptprgasonepossiblemechanismofitsunderexpressionincmlpatientsinthestateofqatar AT mohamedayassin aberrantdnamethylationofptprgasonepossiblemechanismofitsunderexpressionincmlpatientsinthestateofqatar AT govindarajuluvaradharaj aberrantdnamethylationofptprgasonepossiblemechanismofitsunderexpressionincmlpatientsinthestateofqatar AT marziavezzalini aberrantdnamethylationofptprgasonepossiblemechanismofitsunderexpressionincmlpatientsinthestateofqatar AT luisatomasello aberrantdnamethylationofptprgasonepossiblemechanismofitsunderexpressionincmlpatientsinthestateofqatar AT mariamonne aberrantdnamethylationofptprgasonepossiblemechanismofitsunderexpressionincmlpatientsinthestateofqatar AT hishammorsi aberrantdnamethylationofptprgasonepossiblemechanismofitsunderexpressionincmlpatientsinthestateofqatar AT mwalidqoronfleh aberrantdnamethylationofptprgasonepossiblemechanismofitsunderexpressionincmlpatientsinthestateofqatar AT hatemzayed aberrantdnamethylationofptprgasonepossiblemechanismofitsunderexpressionincmlpatientsinthestateofqatar AT richardcook aberrantdnamethylationofptprgasonepossiblemechanismofitsunderexpressionincmlpatientsinthestateofqatar AT claudiosorio aberrantdnamethylationofptprgasonepossiblemechanismofitsunderexpressionincmlpatientsinthestateofqatar AT helmoutmodjtahedi aberrantdnamethylationofptprgasonepossiblemechanismofitsunderexpressionincmlpatientsinthestateofqatar AT naderialdewik aberrantdnamethylationofptprgasonepossiblemechanismofitsunderexpressionincmlpatientsinthestateofqatar |