Asset Details
Do you wish to reserve the book?
Increased local DNA methylation disorder in AMLs with DNMT3A-destabilizing variants and its clinical implication
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Increased local DNA methylation disorder in AMLs with DNMT3A-destabilizing variants and its clinical implication
Do you wish to request the book?
Increased local DNA methylation disorder in AMLs with DNMT3A-destabilizing variants and its clinical implication
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Increased local DNA methylation disorder in AMLs with DNMT3A-destabilizing variants and its clinical implication
2025
Overview
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 niche, and also was a predictor of the response of AML cells to hypomethylating agents, implying that the survival of AML cells depends on stochastic DNA methylations at bivalent domains. Altogether, our work provides a novel mechanistic model suggesting the genomic origin of the aberrant epigenomic heterogeneity in disease conditions.
Through bioinformatic analyses of AML cohorts, Lee et al. explore the association between DNMT3A-destabilizing mutations and increased local concordance of DNA methylation patterns at bivalent domains, and bring insights into their pathological implications.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 45/23
/ 45/61
/ 45/91
/ 49/39
/ 631/114
/ DNA
/ DNA (Cytosine-5-)-Methyltransferases - genetics
/ DNA (Cytosine-5-)-Methyltransferases - metabolism
/ Female
/ Humanities and Social Sciences
/ Humans
/ Leukemia
/ Leukemia, Myeloid, Acute - genetics
/ Leukemia, Myeloid, Acute - pathology
/ Male
/ Mutation
/ Science
