Many of these mutations mapped to DNMT3A regions known to interact with proteins that themselves contribute to AML, such as thymine DNA glycosylase (TDG).
The distinct microRNA expression pattern for DNMT3A R882 AML patients might not only act as markers to predict disease prognosis, but also could be further investigated to develop novel therapeutic targets for patients with DNMT3A mutations.
Genotypic mutation of fms like tyrosine kinase 3 (FLT3), Nucleophosmin (NPM1), and DNA-methyltransferase 3A (DNMT3A) has been involved in the leukemogenesis of acute myeloid leukemia (AML), with the well known poor prognostic role of FLT3 and DNMT3A and favorable role for the NPM1 mutation.
Together, our study demonstrates that Npm1 mutation drives evolution of Dnmt3a-mutant CH to AML and rate of disease progression is accelerated with longer latency of CH.
The DKI mice developed a more aggressive AML with a significantly shortened lifespan and higher percentage of blast cells compared with KI mice expressing Dnmt3a or Nras mutation alone.
In patients with acute myeloid leukemia (AML), 10% to 30% with the normal karyotype express mutations in regulators of DNA methylation, such as TET2 or DNMT3A, in conjunction with activating mutation in the receptor tyrosine kinase FLT3.
The aim was to analyze DNA methylation, hydroxymethylation and mRNA expression profiles in AML with mutations in DNMT3A and IDH1/2 (individually and in combinations).
DNA methyltransferase 3A (DNMT3A) is mutated in various myeloid neoplasms including acute myeloid leukemia (AML), especially at the Arg882 and associated with inferior outcomes.
This report represents the first documentation of the same variant (DNMT3Ap.Arg882His) as both the constitutional mutation associated with TBRS and the somatic mutation hotspot of AML.
Our results provided novel insight into the role of the DNMT3AR882H mutation in AML pathogenesis and suggested that targeting the cellular GSH synthetic pathway could enhance the current therapy for AML patients with the DNMT3AR882H mutation.
DNMT3A mutations are early events during cancer development and seem to confer poor prognosis to acute myeloid leukemia (AML) patients making this gene an attractive target for new therapies.
Mutations in DNMT3A are candidate prognostic and classification markers in adults with acute myeloid leukemia (AML) and T-ALL and thus were considered as candidates prognostic markers in pediatric T-ALL.