Dual inhibition of MDMX and MDM2 as a therapeutic strategy in leukemia

Luis A. Carvajal; Daniela Ben Neriah; Adrien Senecal; Lumie Benard; Victor Thiruthuvanathan; Tatyana Yatsenko; Swathi-Rao Narayanagari; Justin C. Wheat; Tihomira I. Todorova; Kelly Mitchell; Charles Kenworthy; Vincent Guerlavais; D. Allen Annis; Boris Bartholdy; Britta Will; Jesus D. Anampa; Ioannis Mantzaris; Manuel Aivado; Robert H. Singer; Robert A. Coleman; Amit Verma; Ulrich Steidl

doi:10.1126/scitranslmed.aao3003

Research ArticleCancer

Dual inhibition of MDMX and MDM2 as a therapeutic strategy in leukemia

View ORCID ProfileLuis A. Carvajal¹,
Daniela Ben Neriah¹,
View ORCID ProfileAdrien Senecal²,
View ORCID ProfileLumie Benard¹,
View ORCID ProfileVictor Thiruthuvanathan¹,
View ORCID ProfileTatyana Yatsenko¹,
View ORCID ProfileSwathi-Rao Narayanagari¹,³,
View ORCID ProfileJustin C. Wheat¹,
View ORCID ProfileTihomira I. Todorova¹,
View ORCID ProfileKelly Mitchell¹,
Charles Kenworthy²,
Vincent Guerlavais⁴,
D. Allen Annis⁴,
Boris Bartholdy¹,
Britta Will¹,³,⁵,⁶,
View ORCID ProfileJesus D. Anampa⁵,
Ioannis Mantzaris⁵,
Manuel Aivado⁴,
View ORCID ProfileRobert H. Singer²,
View ORCID ProfileRobert A. Coleman²,
Amit Verma³,⁵,⁶ and
View ORCID ProfileUlrich Steidl ¹,³,⁵,⁶,*

¹Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
²Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
³Ruth L. and David S. Gottesman Institute for Stem Cell Research and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
⁴Aileron Therapeutics, Cambridge, MA 02139, USA.
⁵Division of Hemato-Oncology, Department of Medicine (Oncology), Albert Einstein College of Medicine, Bronx, NY 10461, USA.
⁶Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

↵*Corresponding author. Email: ulrich.steidl{at}einstein.yu.edu

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Science Translational Medicine 11 Apr 2018:
Vol. 10, Issue 436, eaao3003
DOI: 10.1126/scitranslmed.aao3003

Luis A. Carvajal

1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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Daniela Ben Neriah

1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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Adrien Senecal

2Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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Lumie Benard

1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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Victor Thiruthuvanathan

1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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Tatyana Yatsenko

1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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Swathi-Rao Narayanagari

1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

3Ruth L. and David S. Gottesman Institute for Stem Cell Research and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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Justin C. Wheat

1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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Tihomira I. Todorova

1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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Kelly Mitchell

1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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Charles Kenworthy

2Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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Vincent Guerlavais

4Aileron Therapeutics, Cambridge, MA 02139, USA.

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D. Allen Annis

4Aileron Therapeutics, Cambridge, MA 02139, USA.

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Boris Bartholdy

1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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Britta Will

1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

3Ruth L. and David S. Gottesman Institute for Stem Cell Research and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

5Division of Hemato-Oncology, Department of Medicine (Oncology), Albert Einstein College of Medicine, Bronx, NY 10461, USA.

6Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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Jesus D. Anampa

5Division of Hemato-Oncology, Department of Medicine (Oncology), Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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Ioannis Mantzaris

5Division of Hemato-Oncology, Department of Medicine (Oncology), Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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Manuel Aivado

4Aileron Therapeutics, Cambridge, MA 02139, USA.

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Robert H. Singer

2Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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Robert A. Coleman

2Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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Amit Verma

3Ruth L. and David S. Gottesman Institute for Stem Cell Research and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

5Division of Hemato-Oncology, Department of Medicine (Oncology), Albert Einstein College of Medicine, Bronx, NY 10461, USA.

6Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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Ulrich Steidl

1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

3Ruth L. and David S. Gottesman Institute for Stem Cell Research and Regenerative Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

5Division of Hemato-Oncology, Department of Medicine (Oncology), Albert Einstein College of Medicine, Bronx, NY 10461, USA.

6Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

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For correspondence: ulrich.steidl@einstein.yu.edu

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Dual inhibition of MDMX and MDM2 as a therapeutic strategy in leukemia

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