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A druggable TCF4- and BRD4-dependent transcriptional network sustains malignancy in blastic plasmacytoid dendritic cell neoplasm

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE75650 | GEO | 2016/11/15

SECONDARY ACCESSION(S): PRJNA304975

REPOSITORIES: GEO

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