GSE79284 | Datasets2Tools

Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition (RNA-seq)

Transcriptomics Dataset

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General Information

Accession	GSE79284
Title	Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition (RNA-seq)
Description	Our study shows that acute myeloid leukemia (AML) cells require the BRD9 subunit of the SWI/SNF chromatin remodeling complex to sustain MYC transcription, rapid cell proliferation, and a block in differentiation. Based on these observations, we derived small-molecule inhibitors of the BRD9 bromodomain, which selectively suppressed the proliferation of mouse and human AML cell lines. To establish these effects as on-target, we engineered a bromodomain-swap allele of BRD9, which retains functionality despite a radically altered bromodomain pocket. Expression of this allele in AML cells conferred resistance to the anti-proliferative effects of our compound series, thus establishing BRD9 as the relevant cellular target. Furthermore, we used an analogous domain-swap strategy to generate an inhibitor-resistant allele of EZH2. Our study provides the first evidence for a role of BRD9 in cancer and reveals a simple genetic strategy for constructing resistance alleles to demonstrate on-target activity of chemical probes in cells.
Landing Page	https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE79284
Repository	Gene 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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