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Transcriptional plasticity promotes primary and acquired resistance to BET inhibition

Author

Listed:
  • 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
    Ludwig Boltzmann Cluster Oncology, Medical University of Vienna)

  • Barbara Peter

    (Medical University of Vienna
    Ludwig Boltzmann Cluster Oncology, 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
    Ludwig Boltzmann Cluster Oncology, 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))

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.

Suggested Citation

  • 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. Bory, 2015. "Transcriptional plasticity promotes primary and acquired resistance to BET inhibition," Nature, Nature, vol. 525(7570), pages 543-547, September.
    • Handle: RePEc:nat:nature:v:525:y:2015:i:7570:d:10.1038_nature14898
    DOI: 10.1038/nature14898
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    Cited by:

    1. Jeannine Diesch & Marguerite-Marie Le Pannérer & René Winkler & Raquel Casquero & Matthias Muhar & Mark van der Garde & Michael Maher & Carolina Martínez Herráez & Joan J. Bech-Serra & Michaela Fellne, 2021. "Inhibition of CBP synergizes with the RNA-dependent mechanisms of Azacitidine by limiting protein synthesis," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    2. Katharine Umphred-Wilson & Shashikala Ratnayake & Qianzi Tang & Rui Wang & Sneha Ghosh Chaudhary & Devaiah N. Ballachanda & Josephine Trichka & Jan Wisniewski & Lan Zhou & Qingrong Chen & Daoud Meerza, 2025. "The ESCRT protein CHMP5 promotes T cell leukemia by enabling BRD4-p300-dependent transcription," Nature Communications, Nature, vol. 16(1), pages 1-19, December.

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