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Aberrant DNA methylation of PTPRG as one possible mechanism of its under‐expression in CML patients in the State of Qatar

Version 3 2024-06-25, 10:30
Version 2 2023-03-19, 05:32
Version 1 2023-03-16, 06:24
journal contribution
revised on 2024-06-25, 10:22 and posted on 2024-06-25, 10:30 authored by 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

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.

Other Information

Published in: Molecular Genetics & Genomic Medicine
License: http://creativecommons.org/licenses/by/4.0/
See article on publisher's website: http://dx.doi.org/10.1002/mgg3.1319

Additional institutions affiliated with: Qatar University, Qatar University Health - QU, College of Health Sciences - QU HEALTH, Biomedical Research Center - QU HEALTH, Qatar Medical Genetic Center - Hamad General Hospital.

Funding

Qatar National Research Fund (28-6-7-17), Novel approach to identify the mechanism(s) of resistance of Chronic Myelocytic Leukaemia to Glivec in a patient population in the State of Qatar.

Qatar National Research Fund (4-157-3–052), Role of Protein Tyrosine Phosphatase Gamma (PTPRG) in the pathogenesis of chronic myeloid leukemia (CML) and its evaluation as a new biomarker of disease.

History

Language

  • English

Publisher

Wiley

Publication Year

  • 2020

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Medical Corporation
  • Academic Health System - HMC
  • Interim Translational Research Institute - HMC
  • Hamad General Hospital - HMC
  • National Center for Cancer Care and Research - HMC
  • Women's Wellness and Research Center - HMC
  • Hamad Bin Khalifa University
  • College of Health and Life Sciences - HBKU
  • World Innovation Summit for Health

Geographic coverage

Qatar

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    Hamad General Hospital - HMC

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