Overcoming adaptive therapy resistance in AML by targeting immune response pathways

Author:

Melgar Katelyn12ORCID,Walker Morgan M.3,Jones LaQuita M.4ORCID,Bolanos Lyndsey C.1,Hueneman Kathleen1ORCID,Wunderlich Mark1ORCID,Jiang Jian-Kang3,Wilson Kelli M.3ORCID,Zhang Xiaohu3,Sutter Patrick3,Wang Amy3,Xu Xin3,Choi Kwangmin1ORCID,Tawa Gregory3ORCID,Lorimer Donald4,Abendroth Jan4ORCID,O’Brien Eric5,Hoyt Scott B.3,Berman Ellin6,Famulare Christopher A.7,Mulloy James C.1,Levine Ross L.678,Perentesis John P.5ORCID,Thomas Craig J.39ORCID,Starczynowski Daniel T.110ORCID

Affiliation:

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

2. Immunology Graduate Program, Cincinnati Children’s Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.

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

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

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

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

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

8. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

9. Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20829, USA.

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

Abstract

Immune stress pathways drive resistance to FLT3 inhibition in FLT3-mutant AML, but a dual inhibitor of FLT3 and IRAK1/4 overcomes this resistance.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

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