Targeting the kinase activities of ATR and ATM exhibits antitumoral activity in mouse models of MLL-rearranged AML

Isabel Morgado-Palacin; Amanda Day; Matilde Murga; Vanesa Lafarga; Marta Elena Anton; Anthony Tubbs; Hua-Tang Chen; Aysegul V. Ergen; Rhonda Anderson; Avinash Bhandoola; Kurt G. Pike; Bernard Barlaam; Elaine Cadogan; Xi Wang; Andrew J. Pierce; Chad Hubbard; Scott A. Armstrong; André Nussenzweig; Oscar Fernandez-Capetillo

doi:10.1126/scisignal.aad8243

Research ArticleCANCER TREATMENT

Targeting the kinase activities of ATR and ATM exhibits antitumoral activity in mouse models of MLL-rearranged AML

Isabel Morgado-Palacin¹,*,
Amanda Day²,*,
Matilde Murga¹,*,
Vanesa Lafarga¹,
Marta Elena Anton¹,
Anthony Tubbs²,
Hua-Tang Chen²,
Aysegul V. Ergen²,
Rhonda Anderson²,
Avinash Bhandoola²,
Kurt G. Pike³,
Bernard Barlaam³,
Elaine Cadogan³,
Xi Wang⁴,
Andrew J. Pierce³,
Chad Hubbard²,
Scott A. Armstrong⁴,
André Nussenzweig²,†, and
Oscar Fernandez-Capetillo¹,⁵,†

¹Genomic Instability Group, Spanish National Cancer Research Center, Madrid 28029, Spain.
²Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
³AstraZeneca, Cambridge CB4 0WG, UK.
⁴Human Oncology and Pathogenesis Program and Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
⁵Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Solna 17165, Sweden.

↵†Corresponding author. Email: ofernandez{at}cnio.es (O.F.-C.); nussenza{at}mail.nih.gov (A.N.)

↵* These authors contributed equally to this work.

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Science Signaling 13 Sep 2016:
Vol. 9, Issue 445, pp. ra91
DOI: 10.1126/scisignal.aad8243

Isabel Morgado-Palacin

1Genomic Instability Group, Spanish National Cancer Research Center, Madrid 28029, Spain.

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Amanda Day

2Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

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Matilde Murga

1Genomic Instability Group, Spanish National Cancer Research Center, Madrid 28029, Spain.

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Vanesa Lafarga

1Genomic Instability Group, Spanish National Cancer Research Center, Madrid 28029, Spain.

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Marta Elena Anton

1Genomic Instability Group, Spanish National Cancer Research Center, Madrid 28029, Spain.

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Anthony Tubbs

2Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

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Hua-Tang Chen

2Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

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Aysegul V. Ergen

2Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

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Rhonda Anderson

2Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

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Avinash Bhandoola

2Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

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Kurt G. Pike

3AstraZeneca, Cambridge CB4 0WG, UK.

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Bernard Barlaam

3AstraZeneca, Cambridge CB4 0WG, UK.

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Elaine Cadogan

3AstraZeneca, Cambridge CB4 0WG, UK.

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Xi Wang

4Human Oncology and Pathogenesis Program and Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

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Andrew J. Pierce

3AstraZeneca, Cambridge CB4 0WG, UK.

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Chad Hubbard

2Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

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Scott A. Armstrong

4Human Oncology and Pathogenesis Program and Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

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André Nussenzweig

2Laboratory of Genome Integrity, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

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For correspondence: ofernandez@cnio.es nussenza@mail.nih.gov

Oscar Fernandez-Capetillo

1Genomic Instability Group, Spanish National Cancer Research Center, Madrid 28029, Spain.

5Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Solna 17165, Sweden.

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For correspondence: ofernandez@cnio.es nussenza@mail.nih.gov

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