Transcriptional plasticity promotes primary and acquired resistance to BET inhibition

Philipp Rathert, Mareike Roth, Tobias Neumann, Felix Muerdter, Jae-Seok Roe, Matthias Muhar, Sumit Deswal, Sabine Cerny-Reiterer, Barbara Peter, Julian Jude, Thomas Hoffmann, Łukasz M. Boryń, Elin Axelsson, Norbert Schweifer, Ulrike Tontsch-Grunt, Lukas E. Dow, Davide Gianni, Mark Pearson, Peter Valent, Alexander Stark, Norbert Kraut, Christopher R. Vakoc and Johannes Zuber ()
Additional contact information
Philipp Rathert: Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC)
Mareike Roth: Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC)
Tobias Neumann: Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC)
Felix Muerdter: Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC)
Jae-Seok Roe: Cold Spring Harbor Laboratory
Matthias Muhar: Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC)
Sumit Deswal: Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC)
Sabine Cerny-Reiterer: Medical University of Vienna
Barbara Peter: Medical University of Vienna
Julian Jude: Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC)
Thomas Hoffmann: Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC)
Łukasz M. Boryń: Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC)
Elin Axelsson: Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC)
Norbert Schweifer: Boehringer Ingelheim – Regional Center Vienna GmbH
Ulrike Tontsch-Grunt: Boehringer Ingelheim – Regional Center Vienna GmbH
Lukas E. Dow: Hematology & Medical Oncology, Weill Cornell Medical College
Davide Gianni: Boehringer Ingelheim – Regional Center Vienna GmbH
Mark Pearson: Boehringer Ingelheim – Regional Center Vienna GmbH
Peter Valent: Medical University of Vienna
Alexander Stark: Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC)
Norbert Kraut: Boehringer Ingelheim – Regional Center Vienna GmbH
Christopher R. Vakoc: Cold Spring Harbor Laboratory
Johannes Zuber: Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC)

Nature, 2015, vol. 525, issue 7570, 543-547

Abstract: BET bromodomain inhibitors are being explored as potential therapeutics in cancer; here, AML cells are shown to evade sensitivity to BET inhibition through rewiring the transcriptional regulation of BRD4 target genes such as MYC in a process that is facilitated by suppression of PRC2 and WNT signalling activation.

Date: 2015
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DOI: 10.1038/nature14898

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