Pluto Bioinformatics

GSE84471: A Druggable TCF4- and BRD4-dependent Transcriptional Network Sustains Malignancy in Blastic Plasmacytoid Dendritic Cell Neoplasm (RNA-Seq)

Bulk RNA sequencing

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. SOURCE: Louis,M.,Staudt (lstaudt@mail.nih.gov) - Louis M Staudt National Cancer Institute