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Series GSE75650 Query DataSets for GSE75650
Status Public on Nov 15, 2016
Title A druggable TCF4- and BRD4-dependent transcriptional network sustains malignancy in blastic plasmacytoid dendritic cell neoplasm
Organism Homo sapiens
Experiment type Expression profiling by array
Summary We combined loss-of-function RNA interference screening and a high-throughput drug toxicity screening to define novel therapeutic targets in blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologic malignancy for which no curative therapy exists. The E-box transcription factor TCF4 emerged as the master transcriptional regulator of the BPDCN oncogenic program, a finding that can be exploited for the accurate molecular diagnosis of BPDCN. Genetic interference with the TCF4-dependent network induced a rewiring of BPDCN gene expression, resulting in apoptosis. Treatment of BPDCN lines with bromodomain and extra-terminal domain inhibitors (BETi's) down regulated TCF4 and its target gene network, inducing apoptosis both in vitro and retarding growth of BPDCN xenografts in vivo, supporting the clinical evaluation of BETi's in this lethal cancer.
Overall design For shRNA gene expression profiling, Cal-1 and Gen2.2 cells were infected with either Ctrl or TCF4 shRNAs. Following puromycin selection, shRNA expression was induced for 24 hours and 48 hours in Cal-1 cells (n=4), and for 12 hours and 24 hours in Gen2.2 cells (n=4). For JQ1 gene expression profiling, Cal-1 (n=4) and Gen2.2 (n=4) cells were treated with either DMSO or 100 nM JQ1 for 1 hour, 3 hours, 8 hours and 24 hours.
Citation(s) 27846392
Submission date Dec 03, 2015
Last update date May 01, 2018
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)
GPL4133 Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version)
GPL16699 Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Feature Number version)
Samples (16)
GSM1961247 Cal-1 shTCF4#1 - 24 hours - mAdbID:118980
GSM1961248 Cal-1 shTCF4#1 - 48 hours - mAdbID:118981
GSM1961249 Cal-1 shTCF4#2 - 24 hours - mAdbID:118982
BioProject PRJNA304975

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Supplementary file Size Download File type/resource
GSE75650_RAW.tar 293.5 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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