Down-regulation of Protein Tyrosine Phosphatase Receptor Gamma (PTPRG) in Chronic Myeloid Leukemia Patients in The State of Qatar is Due to Aberrant DNA Methylation Mechanism

Abstract

Background: Several studies showed that the aberrant DNA methylations are involved in leukemia and cancer pathogenesis. PTPRG is a natural inhibitory mechanism that is found to be down-regulated in Chronic Myeloid Leukemia (CML) disease. The mechanism behind its down-regulation has not been fully elucidated. Aim: The study investigates the role of methylation as a possible mechanism of PTPRG under-expression in CML patients. Method: Peripheral blood samples from CML patients treated with tyrosine kinase inhibitors (TKIs) and healthy controls were collected. DNA was extracted and treated with bisulfite treatment, followed by PCR and sequencing of 25 of CpG in Promoter and 26 of CpG in the Intronic regions of PTPRG. Bisulfite-sequencing technique as a high-resolution method was employed. Results : CML groups (New Diagnosed and Failed treatment) have significantly higher methylation levels in the Promoter and Intron regions compared to the healthy group. There were also significant differences in methylation levels of CpG sites in the Promoter and Intronic regions amongst the groups. Conclusion: Aberrant methylation of PTPRG is documented and potentially is one of the possible mechanisms of PTPRG down-regulation in CML.