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; Jian-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

View ORCID ProfileKatelyn Melgar¹,²,
Morgan M. Walker³,
View ORCID ProfileLaQuita M. Jones⁴,
Lyndsey C. Bolanos¹,
View ORCID ProfileKathleen Hueneman¹,
View ORCID ProfileMark Wunderlich¹,
Jian-Kang Jiang³,
View ORCID ProfileKelli M. Wilson³,
Xiaohu Zhang³,
Patrick Sutter³,
Amy Wang³,
Xin Xu³,
View ORCID ProfileKwangmin Choi¹,
View ORCID ProfileGregory Tawa³,
Donald Lorimer⁴,
View ORCID ProfileJan Abendroth⁴,
Eric O’Brien⁵,
Scott B. Hoyt³,
Ellin Berman⁶,
Christopher A. Famulare⁷,
James C. Mulloy¹,
Ross L. Levine⁶,⁷,⁸,
View ORCID ProfileJohn P. Perentesis⁵,
View ORCID ProfileCraig J. Thomas³,⁹,* and
View ORCID ProfileDaniel 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

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.

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ORCID record for Katelyn Melgar

Morgan M. Walker

3Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.

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LaQuita M. Jones

4UCB Bainbridge, Bainbridge Island, WA 98110, USA.

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Lyndsey C. Bolanos

1Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.

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Kathleen Hueneman

1Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.

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ORCID record for Kathleen Hueneman

Mark Wunderlich

1Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.

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Jian-Kang Jiang

3Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.

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Kelli M. Wilson

3Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.

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ORCID record for Kelli M. Wilson

Xiaohu Zhang

3Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.

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Patrick Sutter

3Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.

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Amy Wang

3Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.

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Xin Xu

3Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.

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Kwangmin Choi

1Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.

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Gregory Tawa

3Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.

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Donald Lorimer

4UCB Bainbridge, Bainbridge Island, WA 98110, USA.

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Jan Abendroth

4UCB Bainbridge, Bainbridge Island, WA 98110, USA.

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Eric O’Brien

5Division of Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.

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Scott B. Hoyt

3Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.

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Ellin Berman

6Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

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Christopher A. Famulare

7Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

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James C. Mulloy

1Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.

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Ross L. Levine

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.

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John P. Perentesis

5Division of Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.

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Craig J. Thomas

3Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD 20892, USA.

9Lymphoid 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

1Division of Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.

10Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.

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ORCID record for Daniel T. Starczynowski
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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