Increased local DNA methylation disorder in AMLs with DNMT3A-destabilizing variants and its clinical implication.

ABSTRACT: The mechanistic link between the complex mutational landscape of de novo methyltransferase DNMT3A and the pathology of acute myeloid leukemia (AML) has not been clearly elucidated so far. Motivated by a recent discovery of the significance of DNMT3A-destabilizing mutations (DNMT3A^INS) in AML, we here investigate the common characteristics of DNMT3A^INS AML methylomes through computational analyses. We present that methylomes of DNMT3A^INS AMLs are considerably different from those of DNMT3A^R882 AMLs in that they exhibit increased intratumor DNA methylation heterogeneity in bivalent chromatin domains. This epigenetic heterogeneity was associated with the transcriptional variability of developmental and membrane-associated factors shaping stem cell n

SUBMITTER: Lee D 

PROVIDER: S-EPMC11724044 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature