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Series GSE84471 Query DataSets for GSE84471
Status Public on Nov 15, 2016
Title A Druggable TCF4- and BRD4-dependent Transcriptional Network Sustains Malignancy in Blastic Plasmacytoid Dendritic Cell Neoplasm (RNA-Seq)
Organism Homo sapiens
Experiment type Expression 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 RNA sequencing (RNA-Seq) on the 6 FFPE BPDCN biopsies for which the FFPE RNA was not excessively degraded. Because only one PHN and none of the primary AML cases passed the RNA QC for library generation, we embedded BPDCN cell lines (Cal-1 and Gen2.2) and AML cell lines (HL-60, MOLM-14 and SKM-1) in paraffin blocks after formalin fixation, and used the FFPE RNA-Seq from these cell lines as a compare/contrast control.
Citation(s) 27846392
Submission date Jul 15, 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 (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (14)
GSM2236841 Cal-1 RNA-Seq
GSM2236842 Gen2.2 RNA-Seq
GSM2236843 Cal-1 FFPE RNA-Seq
BioProject PRJNA329312
SRA SRP078597

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Supplementary file Size Download File type/resource
GSE84471_RNA-Seq_FFPE_BPDCN_Normalized.xls.gz 1.9 Mb (ftp)(http) XLS
GSE84471_RNA-Seq_pDCs_vs_BPDCN_cell_lines_normalized.xlsx 2.3 Mb (ftp)(http) XLSX
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