Methylation Analysis of SOX2 gene in AML and ALL patients by Bisulfite Medification

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Muhammad Usman, Iftikhar Ahmad, Shafiq ur Rehman, Abdul Hafeez, Nadeem Ullah, Sadia Zulfiqar, Muhammad Asam Raza


Epigenetic modifications play a crucial role in the regulation of gene expression. Methylation is one of the most important players that determines the fate of gene expression and renders a fundamental role in the regulation of stem cell pluripotency. SOX2 is an important transcription factor that plays a key role in maintaining stem cell pluripotency. Aberrant methylation in the promoter region of SOX2 disrupts the normal cellular differentiation. The present study aimed to assess the methylation status of CpG islands in the promoter region of SOX2 gene in AML and ALL patients. This gene is unmethylated in human embryonic stem cells, whereas it is shown to be partially methylated in AML and ALL. Methylation profile of SOX2 gene was analyzed in 50 samples each of Acute Myeloid Leukemia, Acute Lymphocytic Leukemia and control samples. DNA samples of AML and ALL were modified with sodium bisulfite. Successful completion of bisulfite modification was confirmed by amplifying the bisulfite treated samples by Methylation-specific PCR. Few of the samples showed amplification with methylated primer and others with unmethylated primer, however majority of the patient samples showed partial methylation at the CpG islands of SOX2 gene. 29 out of 50 ALL patients and 30 out of 50 AML showed amplification with both methylated and unmethylated primers, that represent partial methylation. These findings suggest that aberrant methylation in the promoter region of SOX2 gene contributes to leukemogenesis. Furthermore, it was found that males are more prone to AML and ALL as compared to females. More studies are required to scrutinize the detailed methylation profile of SOX2 gene in AML and ALL patients. Aberrant methylation of SOX2 presents a potent therapeutic target for future therapy of AML and ALL.

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