DNA methylation at cystosine residues is a crucial epigenetic modification that regulates gene expression to control cell proliferation and differentiation. Dysregulation of this methylation due to overexpression of DNMT3A or inactivation of TET2 can result in aberrant regional DNA hypermethylation. This drives myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) pathogenesis by transcriptionally repressing tumor suppressor genes or by displacing CTCF proteins, resulting in aberrant expression of oncogenes.
DNMT3A is a methyltransferase that is often mutated in MDS/AML.
Inactivation of the methyltransferase TET2 is one of the most frequent drivers of MDS/AML.
Watch out for changes in levels of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC), resulting from overexpression of DNMT3A or inactivation of TET2.