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Heterodimeric JAK–STAT activation as a mechanism of persistence to JAK2 inhibitor therapy

Author

Listed:
  • Priya Koppikar

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center)

  • Neha Bhagwat

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
    Gerstner Sloan- Kettering Graduate School in Biomedical Sciences, Memorial Sloan-Kettering Cancer Center)

  • Outi Kilpivaara

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center)

  • Taghi Manshouri

    (M. D. Anderson Cancer Center)

  • Mazhar Adli

    (Howard Hughes Medical Institute, Massachusetts General Hospital and Broad Institute of Harvard, Massachusetts Institute of Technology)

  • Todd Hricik

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center)

  • Fan Liu

    (Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center)

  • Lindsay M. Saunders

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
    Gerstner Sloan- Kettering Graduate School in Biomedical Sciences, Memorial Sloan-Kettering Cancer Center)

  • Ann Mullally

    (Brigham and Women’s Hospital, Harvard Medical School)

  • Omar Abdel-Wahab

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
    Leukemia Service, Memorial Sloan-Kettering Cancer Center)

  • Laura Leung

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center)

  • Abby Weinstein

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center)

  • Sachie Marubayashi

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center)

  • Aviva Goel

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center)

  • Mithat Gönen

    (Memorial Sloan-Kettering Cancer Center)

  • Zeev Estrov

    (M. D. Anderson Cancer Center)

  • Benjamin L. Ebert

    (Brigham and Women’s Hospital, Harvard Medical School)

  • Gabriela Chiosis

    (Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center)

  • Stephen D. Nimer

    (Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center
    Leukemia Service, Memorial Sloan-Kettering Cancer Center)

  • Bradley E. Bernstein

    (Howard Hughes Medical Institute, Massachusetts General Hospital and Broad Institute of Harvard, Massachusetts Institute of Technology)

  • Srdan Verstovsek

    (M. D. Anderson Cancer Center)

  • Ross L. Levine

    (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
    Leukemia Service, Memorial Sloan-Kettering Cancer Center)

Abstract

Chronic exposure to JAK2 inhibitors leads to reactivation of downstream signalling through the formation of heterodimers between JAK2 and other JAK kinases in myeloproliferative neoplasms, which can be overcome with Hsp90 inhibitors.

Suggested Citation

  • Priya Koppikar & Neha Bhagwat & Outi Kilpivaara & Taghi Manshouri & Mazhar Adli & Todd Hricik & Fan Liu & Lindsay M. Saunders & Ann Mullally & Omar Abdel-Wahab & Laura Leung & Abby Weinstein & Sachie , 2012. "Heterodimeric JAK–STAT activation as a mechanism of persistence to JAK2 inhibitor therapy," Nature, Nature, vol. 489(7414), pages 155-159, September.
    • Handle: RePEc:nat:nature:v:489:y:2012:i:7414:d:10.1038_nature11303
    DOI: 10.1038/nature11303
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    Cited by:

    1. Hongxing Shen & Fengyuan Huang & Xiangmin Zhang & Oluwagbemiga A. Ojo & Yuebin Li & Hoa Quang Trummell & Joshua C. Anderson & John Fiveash & Markus Bredel & Eddy S. Yang & Christopher D. Willey & Zech, 2022. "Selective suppression of melanoma lacking IFN-γ pathway by JAK inhibition depends on T cells and host TNF signaling," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Zijian Fang & Giuditta Corbizi Fattori & Thomas McKerrell & Rebecca H. Boucher & Aimee Jackson & Rachel S. Fletcher & Dorian Forte & Jose-Ezequiel Martin & Sonia Fox & James Roberts & Rachel Glover & , 2023. "Tamoxifen for the treatment of myeloproliferative neoplasms: A Phase II clinical trial and exploratory analysis," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    3. Hidehiro Itonaga & Adnan K. Mookhtiar & Sarah M. Greenblatt & Fan Liu & Concepcion Martinez & Daniel Bilbao & Masai Rains & Pierre-Jacques Hamard & Jun Sun & Afoma C. Umeano & Stephanie Duffort & Chua, 2024. "Tyrosine phosphorylation of CARM1 promotes its enzymatic activity and alters its target specificity," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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