The SIGnaling Network
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Pathway ID: SIGNOR-AML-DNMT3A

Description: In de novo AML, without cytogenetic aberrations, somatic missense mutations of the DNA methyltransferase 3A (DNMT3A) have been frequently (22%) reported. Mammalian DNA methyltransferases (DNMTs) catalyze the transfer of a methyl group onto the 5′-position of cytosine at CpG dinucleotides. DNA methylation regulates the expression of oncogenes and tumor-suppressor genes. DNMT3A forms homo- and heterotetrameric complexes, therefore, mutations in DNMT3A can directly alter DNMT3A function or change the enzyme interaction with partner proteins. In fact, some DNMT3A mutants show enhanced activity, while others show attenuated ability, to methylate target genes.Loss of function of DNMT3A (the best characterized is the mutation R882H) may cause focal promoter hypomethylation, associated to transcriptional reactivation of the leukemogenic HOX cofactor MEIS1 and homeobox genes. On the other end, a subset of AML mutations of DNMT3 display enhanced ability to perform an aberrant, non-CpG methylation, associated with maintaining pluripotency. PMID:26434589; PMID:30705090

Curated by: irozzo