Inhibition of mitochondrial translation overcomes venetoclax resistance in AML through activation of the integrated stress response

David Sharon; Severine Cathelin; Sara Mirali; Justin M. Di Trani; David J. Yanofsky; Kristine A. Keon; John L. Rubinstein; Aaron D. Schimmer; Troy Ketela; Steven M. Chan

doi:10.1126/scitranslmed.aax2863

Research ArticleCancer

Inhibition of mitochondrial translation overcomes venetoclax resistance in AML through activation of the integrated stress response

David Sharon¹,
Severine Cathelin¹,
Sara Mirali¹,
Justin M. Di Trani²,
David J. Yanofsky²,³,
Kristine A. Keon²,³,
John L. Rubinstein²,³,
Aaron D. Schimmer¹,³,
Troy Ketela¹ and
Steven M. Chan ¹,³,*

¹Princess Margaret Cancer Centre, Toronto, Ontario M5G 1L7, Canada.
²Molecular Medicine Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.
³Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7, Canada.

↵*Corresponding author. Email: steven.chan{at}uhnresearch.ca

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Science Translational Medicine 30 Oct 2019:
Vol. 11, Issue 516, eaax2863
DOI: 10.1126/scitranslmed.aax2863

David Sharon

Princess Margaret Cancer Centre, Toronto, Ontario M5G 1L7, Canada.

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Severine Cathelin

Princess Margaret Cancer Centre, Toronto, Ontario M5G 1L7, Canada.

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Sara Mirali

Princess Margaret Cancer Centre, Toronto, Ontario M5G 1L7, Canada.

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Justin M. Di Trani

Molecular Medicine Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.

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David J. Yanofsky

Molecular Medicine Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7, Canada.

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Kristine A. Keon

Molecular Medicine Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7, Canada.

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John L. Rubinstein

Molecular Medicine Program, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7, Canada.

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Aaron D. Schimmer

Princess Margaret Cancer Centre, Toronto, Ontario M5G 1L7, Canada.Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7, Canada.

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Troy Ketela

Princess Margaret Cancer Centre, Toronto, Ontario M5G 1L7, Canada.

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Steven M. Chan

Princess Margaret Cancer Centre, Toronto, Ontario M5G 1L7, Canada.Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7, Canada.

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For correspondence: steven.chan@uhnresearch.ca

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Inhibition of mitochondrial translation overcomes venetoclax resistance in AML through activation of the integrated stress response

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