Overcoming adaptive therapy resistance in AML by targeting immune response pathways

Katelyn Melgar; Morgan M. Walker; LaQuita M. Jones; Lyndsey C. Bolanos; Kathleen Hueneman; Mark Wunderlich; Jiang-Kang Jiang; Kelli M. Wilson; Xiaohu Zhang; Patrick Sutter; Amy Wang; Xin Xu; Kwangmin Choi; Gregory Tawa; Donald Lorimer; Jan Abendroth; Eric O’Brien; Scott B. Hoyt; Ellin Berman; Christopher A. Famulare; James C. Mulloy; Ross L. Levine; John P. Perentesis; Craig J. Thomas; Daniel T. Starczynowski

doi:10.1126/scitranslmed.aaw8828

Research ArticleCancer

Overcoming adaptive therapy resistance in AML by targeting immune response pathways

Katelyn Melgar¹,²,
Morgan M. Walker³,
LaQuita M. Jones⁴,
Lyndsey C. Bolanos¹,
Kathleen Hueneman¹,
Mark Wunderlich¹,
Jiang-Kang Jiang³,
Kelli M. Wilson³,
Xiaohu Zhang³,
Patrick Sutter³,
Amy Wang³,
Xin Xu³,
Kwangmin Choi¹,
Gregory Tawa³,
Donald Lorimer⁴,
Jan Abendroth⁴,
Eric O’Brien⁵,
Scott B. Hoyt³,
Ellin Berman⁶,
Christopher A. Famulare⁷,
James C. Mulloy¹,
Ross L. Levine⁶,⁷,⁸,
John P. Perentesis⁵,
Craig J. Thomas³,⁹,* and
Daniel T. Starczynowski¹,¹⁰,*

¹Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.
²Immunology Graduate Program, Cincinnati Children’s Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
³Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.
⁴UCB Bainbridge, Bainbridge Island, WA 98110, USA.
⁵Division of Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.
⁶Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
⁷Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
⁸Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
⁹Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20829, USA.
¹⁰Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.

↵*Corresponding author. Email: craigt{at}mail.nih.gov (C.J.T.); daniel.starczynowski{at}cchmc.org (D.T.S.)

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Science Translational Medicine 04 Sep 2019:
Vol. 11, Issue 508, eaaw8828
DOI: 10.1126/scitranslmed.aaw8828

Katelyn Melgar

Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.Immunology Graduate Program, Cincinnati Children’s Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.

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Morgan M. Walker

Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.

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LaQuita M. Jones

UCB Bainbridge, Bainbridge Island, WA 98110, USA.

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Lyndsey C. Bolanos

Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.

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Kathleen Hueneman

Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.

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Mark Wunderlich

Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.

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Jiang-Kang Jiang

Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.

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Kelli M. Wilson

Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.

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Xiaohu Zhang

Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.

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Patrick Sutter

Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.

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Amy Wang

Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.

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Xin Xu

Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.

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Kwangmin Choi

Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.

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Gregory Tawa

Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.

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Donald Lorimer

UCB Bainbridge, Bainbridge Island, WA 98110, USA.

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Jan Abendroth

UCB Bainbridge, Bainbridge Island, WA 98110, USA.

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Eric O’Brien

Division of Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.

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Scott B. Hoyt

Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.

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Ellin Berman

Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

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Christopher A. Famulare

Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

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James C. Mulloy

Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.

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Ross L. Levine

Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

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John P. Perentesis

Division of Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.

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Craig J. Thomas

Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20829, USA.

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For correspondence: craigt@mail.nih.gov daniel.starczynowski@cchmc.org

Daniel T. Starczynowski

Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.

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For correspondence: craigt@mail.nih.gov daniel.starczynowski@cchmc.org

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Overcoming adaptive therapy resistance in AML by targeting immune response pathways

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