Unrevealing the Epigenetic Landscape: SOX-2 and OCT-4 methylation in acute myeloid leukemia and myelodysplastic neoplasm

DISCOVERIES (ISSN 2359-7232), 2026, Volume 14, Issue 2

_{Original Article - Case Report}

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_{CITATION: Singh et al. T Unrevealing the Epigenetic Landscape: SOX-2 and OCT-4 methylation in acute myeloid leukemia and myelodysplastic neoplasm. Discoveries 2026, Apr-Jun, 14(2): e229. DOI: 10.15190/d.2026.8}

_{Unrevealing the Epigenetic Landscape: SOX-2 and OCT-4 methylation in acute myeloid leukemia and myelodysplastic neoplasm}

Damini Singh¹, Manish Kumar², Geeta Yadav^3, *, Uma Shankar Singh³, Shantanu Prakash⁴, Rashmi Kushwaha³, Mili Jain³, Shailendra Prasad Verma²

¹ Department of Pathology, Autonomous State Medical College, Hardoi, India

² Department of Clinical Hematology, King George's Medical University, Lucknow, India

³ Department of Pathology, King George's Medical University, Lucknow, India

⁴ Precision Medicine Unit, Department of Critical Care Medicine, King George's Medical University, Lucknow, UP, India

¹Corresponding author: Dr. Geeta Yadav, MD, PDCC, MNAMS, Additional professor, Department of Pathology, KGMU, Lucknow, UP, India; E-mail: drgeetayadav6@gmail.com; Phone number: +919795199085

_Abstract

Epigenetic modifications, particularly aberrant DNA methylation, play an important role in the pathogenesis of both solid and hematologic malignancies. Global hypomethylation and promoter hypermethylation can silence numerous tumor suppressor genes identified in acute myeloid leukemia (AML) and myelodysplastic neoplasm (MDS). Among stemness-associated transcription factors, OCT-4 and SOX-2 are key regulators of pluripotency and stem cell maintenance and have been implicated in cancer stem cell biology and tumor progression. Although their abnormal expression and epigenetic regulation have been reported in various malignancies, limited data are available regarding their promoter methylation status specifically in AML and MDS. Therefore, this study aimed to evaluate the methylation patterns of the transcription factors, specifically OCT-4 and SOX-2, in patients with AML and MDS. The study involved 84 newly diagnosed AML and MDS patients and 16 age, and sex-matched healthy controls. DNA was extracted from blood or bone marrow using a QIAGEN RDNA extraction kit. The SOX-2 and OCT-4 genes were studied using PCR-specific primers for methylated and unmethylated targets. SOX-2 gene methylation was observed in a significantly higher proportion of AML (n=48/77) and MDS (n=4/7) as compared to Controls (n=3/16) (p<0.001). OCT-4 methylation was also observed in a significantly higher proportion of AML (n=44/77) as compared to MDS (n=3/7) and Controls (n=1/16) (p<0.001). Only a few cases in the AML group had both SOX-2 and OCT-4 gene methylation (n=25/77), compared with MDS (n=0/7) and Controls (n=0/16) (p<0.007). This study indicates that SOX-2 and OCT-4 gene methylation is significantly more prevalent in AML and MDS patients than healthy controls, suggesting their potential involvement in leukemogenesis. These findings highlight the potential role of methylation of stemness-associated transcription factors as a biomarker for disease characterization and identification of epigenetic therapeutic targets in AML and MDS.

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