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An Unexpected Chink in the Transcriptional Armor of Plasmacytoid Dendritic Neoplasms
Maria Kleppe, Ross L. Levine Cancer Cell Volume 30, Issue 5, Pages (November 2016) DOI: /j.ccell Copyright © 2016 Elsevier Inc. Terms and Conditions
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Figure 1 Roadmap to a Druggable BPDCN-Specific Transcriptional Network
Comprehensive genomic and functional investigation of BPDCN cells leads to the identification of a TCF4/BRD4-dependent regulatory network that sustains the BPDCN tumor phenotype and can be targeted by BET protein inhibitors. shRNA screening identified TCF4 and BRD4 among top hits, and drug screening identified toxicity induced by BET inhibitors such as JQ1 in BPDCN. RNA-seq, ChIP-seq, and ATAC-seq identified genes regulated by TCF4-bound super-enhancers in BPDCN and showed that BRD4 is important for TCF4 transcriptional activity. BPDCN, blastic plasmacytoid dendritic cell neoplasm; HTS, high-throughput screening; SEs, super-enhancers; pDCs, plasmacytoid dendritic cells; cDCs, classical dendritic cells; AML, acute myeloid leukemia. Cancer Cell , DOI: ( /j.ccell ) Copyright © 2016 Elsevier Inc. Terms and Conditions
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