Nature Communications (Jun 2019)
Targeting enhancer switching overcomes non-genetic drug resistance in acute myeloid leukaemia
- Charles C. Bell,
- Katie A. Fennell,
- Yih-Chih Chan,
- Florian Rambow,
- Miriam M. Yeung,
- Dane Vassiliadis,
- Luis Lara,
- Paul Yeh,
- Luciano G. Martelotto,
- Aljosja Rogiers,
- Brandon E. Kremer,
- Olena Barbash,
- Helai P. Mohammad,
- Timothy M. Johanson,
- Marian L. Burr,
- Arindam Dhar,
- Natalie Karpinich,
- Luyi Tian,
- Dean S. Tyler,
- Laura MacPherson,
- Junwei Shi,
- Nathan Pinnawala,
- Chun Yew Fong,
- Anthony T. Papenfuss,
- Sean M. Grimmond,
- Sarah-Jane Dawson,
- Rhys S. Allan,
- Ryan G. Kruger,
- Christopher R. Vakoc,
- David L. Goode,
- Shalin H. Naik,
- Omer Gilan,
- Enid Y. N. Lam,
- Jean-Christophe Marine,
- Rab K. Prinjha,
- Mark A. Dawson
Affiliations
- Charles C. Bell
- Cancer Research Division, Peter MacCallum Cancer Centre
- Katie A. Fennell
- Cancer Research Division, Peter MacCallum Cancer Centre
- Yih-Chih Chan
- Cancer Research Division, Peter MacCallum Cancer Centre
- Florian Rambow
- Laboratory for Molecular Cancer Biology, VIB Center for Cancer Biology, KU Leuven
- Miriam M. Yeung
- Cancer Research Division, Peter MacCallum Cancer Centre
- Dane Vassiliadis
- Cancer Research Division, Peter MacCallum Cancer Centre
- Luis Lara
- Cancer Research Division, Peter MacCallum Cancer Centre
- Paul Yeh
- Cancer Research Division, Peter MacCallum Cancer Centre
- Luciano G. Martelotto
- Centre for Cancer Research, University of Melbourne
- Aljosja Rogiers
- Laboratory for Molecular Cancer Biology, VIB Center for Cancer Biology, KU Leuven
- Brandon E. Kremer
- Epigenetics DPU, GlaxoSmithKline
- Olena Barbash
- Epigenetics DPU, GlaxoSmithKline
- Helai P. Mohammad
- Epigenetics DPU, GlaxoSmithKline
- Timothy M. Johanson
- The Walter and Eliza Hall Institute of Medical Research
- Marian L. Burr
- Cancer Research Division, Peter MacCallum Cancer Centre
- Arindam Dhar
- Epigenetics DPU, GlaxoSmithKline
- Natalie Karpinich
- Epigenetics DPU, GlaxoSmithKline
- Luyi Tian
- The Walter and Eliza Hall Institute of Medical Research
- Dean S. Tyler
- Cancer Research Division, Peter MacCallum Cancer Centre
- Laura MacPherson
- Cancer Research Division, Peter MacCallum Cancer Centre
- Junwei Shi
- Perelman School of Medicine, University of Pennsylvania
- Nathan Pinnawala
- Cancer Research Division, Peter MacCallum Cancer Centre
- Chun Yew Fong
- Cancer Research Division, Peter MacCallum Cancer Centre
- Anthony T. Papenfuss
- Cancer Research Division, Peter MacCallum Cancer Centre
- Sean M. Grimmond
- Centre for Cancer Research, University of Melbourne
- Sarah-Jane Dawson
- Cancer Research Division, Peter MacCallum Cancer Centre
- Rhys S. Allan
- The Walter and Eliza Hall Institute of Medical Research
- Ryan G. Kruger
- Epigenetics DPU, GlaxoSmithKline
- Christopher R. Vakoc
- Cold Spring Harbor Laboratory, Cold Spring Harbor
- David L. Goode
- Cancer Research Division, Peter MacCallum Cancer Centre
- Shalin H. Naik
- The Walter and Eliza Hall Institute of Medical Research
- Omer Gilan
- Cancer Research Division, Peter MacCallum Cancer Centre
- Enid Y. N. Lam
- Cancer Research Division, Peter MacCallum Cancer Centre
- Jean-Christophe Marine
- Laboratory for Molecular Cancer Biology, VIB Center for Cancer Biology, KU Leuven
- Rab K. Prinjha
- Epigenetics DPU, GlaxoSmithKline
- Mark A. Dawson
- Cancer Research Division, Peter MacCallum Cancer Centre
- DOI
- https://doi.org/10.1038/s41467-019-10652-9
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 15
Abstract
There is increasing evidence that epigenetic mechanisms contribute to therapeutic resistance in cancer. Here the authors study AML patient samples and a mouse model of non-genetic resistance and find that transcriptional plasticity drives stable epigenetic resistance, and identify regulators of enhancer function as important modulators of resistance.
