DNMT3A R882 mutations promote anthacyline resistance through impaired DNA-damage sensing [RNA-Seq]
Transcriptomics Dataset
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General Information
AccessionGSE72737
TitleDNMT3A R882 mutations promote anthacyline resistance through impaired DNA-damage sensing [RNA-Seq]
DescriptionAlthough the majority of acute myeloid leukemia (AML) patients initially respond to chemotherapy, most of them subsequently relapse due to persistent, chemoresistant disease. However, the mechanistic basis by which AML cells persist during chemotherapy has not been fully delineated. Recurrent somatic mutations in the DNA methyltransferase 3A gene (DNMT3A), most frequently at arginine 882 (DNMT3Amut), are commonly observed in AML patients, and are also detected in elderly subjects with clonal hematopoiesis in the absence of leukemic transformation. DNMT3Amut AML patients have an inferior outcome when treated with standard dose daunorubicin-based induction chemotherapy, suggesting that DNMT3Amut AML cells can persist following chemotherapy and drive relapse. DNMT3Amut cells show impaired nucleosome eviction and chromatin remodeling in response to DNA damage in the setting of anthracycline exposure. This defect leads to an inability to sense and repair DNA damage, which results in the accumulation of single-stranded DNA breaks and increased mutagenesis. Our studies identify a critical role for DNMT3A R882 mutations in driving AML chemoresistance, and highlight the importance of chromatin remodeling in the response to cytotoxic chemotherapy.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE72737
RepositoryGene Expression Omnibus
Tools used to analyze the dataset
Dataset Accession
ARCHS4
Published September 2017
ARCHS4 provides access to gene counts from HiSeq 2000 and HiSeq 2500 platforms for human and mouse experiments from GEO ...
4645
Clustergrammer
Published October 2017
Web-based tool for visualizing and analyzing high-dimensional data as interactive and shareable heatmaps
4645
Canned Analyses generated with the dataset
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Interactive heatmap visualization of RNA-seq dataset GSE72737
ARCHS4, Clustergrammer
Highly interactive web-based heatmap visualization of the top 500 most variable genes in t...
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