Methylation of the MAPK1 Gene as a Potential Diagnostic and Prognostic Biomarker in Childhood B-Acute Lymphoblastic Leukemia

Abstract

Background: Acute lymphoblastic leukemia is a type of heterogeneous leukemia that is associated with the abnormal proliferation of immature monoclonal B and T lymphoid precursors. Cancer is considered an epigenetic disease due to fundamental changes in the pattern of normal methylation in cancer cells. This study aimed to investigate these changes in 5 candidate genes in childhood B cell-ALL.

Materials and Methods: After blood sampling, DNA extraction, and bisulfite treatment, PCR, and Sanger sequencing were performed for part of the TBX3, SLC38A11, SOX2, KCNQ1, and MAPK1 gene promoter. Finally, the methylation pattern of patients in remission and relapse groups was compared with that of healthy individuals.

Results: In the promoter methylation pattern of MAPK1, a significant difference was observed in the CpG3 site between remission-control and relapse-control groups, and in CpG8, 9, 10 between relapse-control and relapse-remission groups. There was no significant difference in the other 4 genes. 

Conclusion: We reported the similarity of the methylation pattern in the CpG 3 site of the MAPK1 gene promoter in the remission and relapse groups, as well as the difference in the methylation pattern of this location in the two mentioned groups with control groups, which can suggest the methylation pattern in this site as a candidate for a prognostic biomarker. We also reported the similarity of methylation pattern in remission and control groups on CpG 8,9,10 site and significant reduction of methylation in the relapse group compared to both control and remission groups, which can introduce them as a candidate for diagnostic biomarkers.