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Series GSE84623 Query DataSets for GSE84623
Status Public on Nov 15, 2016
Title A Druggable TCF4- and BRD4-dependent Transcriptional Network Sustains Malignancy in Blastic Plasmacytoid Dendritic Cell Neoplasm (ATAC-Seq)
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive and largely incurable hematologic malignancy originating from plasmacytoid dendritic cells (pDCs). Using RNA interference screening, we identified the E-box transcription factor TCF4 as a master regulator of the BPDCN oncogenic program. TCF4 served as a faithful diagnostic marker of BPDCN, and its downregulation caused the loss of the BPDCN-specific expression program and apoptosis. High-throughput drug screening revealed that bromodomain and extra-terminal domain inhibitors (BETi's) induce BPDCN apoptosis, which was attributable to disruption of the TCF4-dependent transcriptional network and loss of BPDCN-specific super-enhancers. BETi's retarded the growth of BPDCN xenografts, supporting their clinical evaluation in this recalcitrant malignancy.
Overall design We performed ATAC-Seq to measure chromatin accessibility in normal pDCs (n=2) and primary BPDCN (n=1), together with BPDCN cell lines (Cal-1 and Gen2.2) (n=2), AML cell lines (HL-60 and MOLM-14) (n=2) and conventional myeloid DCs (n=2) as specificity controls.
Citation(s) 27846392
Submission date Jul 20, 2016
Last update date May 15, 2019
Contact name Louis M. Staudt
Phone 301-402-1892
Organization name National Cancer Institute
Department Lymphoid Malignancies Branch
Lab Louis M Staudt
Street address 9000 Rockville Pike, Bldg 10, Rm 4N114
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (9)
GSM2243033 Cal-1 ATAC-Seq
GSM2243034 Gen2.2 ATAC-Seq
GSM2243035 HL-60 ATAC-Seq
BioProject PRJNA330681
SRA SRP078993

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE84623_RAW.tar 95.8 Mb (http)(custom) TAR (of WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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