| Literature DB >> 27846392 |
Michele Ceribelli1, Zhiying Esther Hou2, Priscilla N Kelly3, Da Wei Huang3, George Wright4, Karthik Ganapathi5, Moses O Evbuomwan5, Stefania Pittaluga5, Arthur L Shaffer3, Guido Marcucci6, Stephen J Forman6, Wenming Xiao7, Rajarshi Guha8, Xiaohu Zhang8, Marc Ferrer8, Laurence Chaperot9, Joel Plumas9, Elaine S Jaffe5, Craig J Thomas8, Boris Reizis10, Louis M Staudt11.
Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive and largely incurable hematologic malignancy originating from plasmacytoid dendritic cells (pDCs). Using RNAi 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 gene expression program and apoptosis. High-throughput drug screening revealed that bromodomain and extra-terminal domain inhibitors (BETis) induced BPDCN apoptosis, which was attributable to disruption of a BPDCN-specific transcriptional network controlled by TCF4-dependent super-enhancers. BETis retarded the growth of BPDCN xenografts, supporting their clinical evaluation in this recalcitrant malignancy. Published by Elsevier Inc.Entities:
Keywords: BPDCN; BRD4; HTS; TCF4; super-enhancer
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Year: 2016 PMID： 27846392 PMCID： PMC5175469 DOI： 10.1016/j.ccell.2016.10.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743