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

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 Marubayashi, Aviva Goel, Mithat Gönen, Zeev Estrov, Benjamin L. Ebert, Gabriela Chiosis, Stephen D. Nimer, Bradley E. Bernstein, Srdan Verstovsek and Ross L. Levine ()
Additional contact information
Priya Koppikar: Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center
Neha Bhagwat: Human Oncology and Pathogenesis Program, 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
Ann Mullally: Brigham and Women’s Hospital, Harvard Medical School
Omar Abdel-Wahab: Human Oncology and Pathogenesis Program, 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
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

Nature, 2012, vol. 489, issue 7414, 155-159

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.

Date: 2012
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DOI: 10.1038/nature11303

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