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

Nature

Volumn 489, Issue 7414, 2012, Pages 155-159

  Koppikar, Priya ^a   Bhagwat, Neha ^a   Kilpivaara, Outi ^a   Manshouri, Taghi ^b   Adli, Mazhar ^c   Hricik, Todd ^a   Liu, Fan ^a   Saunders, Lindsay M ^a   Mullally, Ann ^d   Abdel Wahab, Omar ^a   Leung, Laura ^a   Weinstein, Abby ^a   Marubayashi, Sachie ^a   Goel, Aviva ^a   Gonen, Mithat ^a   Estrov, Zeev ^b   Ebert, Benjamin L ^d   Chiosis, Gabriela ^a   Nimer, Stephen D ^a   Bernstein, Bradley E ^c   Verstovsek, Srdan ^b   Levine, Ross L ^a   more..

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^c MASSACHUSETTS GENERAL HOSPITAL   (United States)

^d BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

JANUS KINASE 1; JANUS KINASE 2; METHYLCELLULOSE; PROTEIN KINASE TYK2; RUXOLITINIB; STAT PROTEIN; HEAT SHOCK PROTEIN 90;

CELL ORGANELLE; ENZYME ACTIVITY; GENE EXPRESSION; INHIBITION; INHIBITOR; PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER CELL CULTURE; CONTROLLED STUDY; DIMERIZATION; DISEASE MODEL; ENZYME ACTIVATION; ENZYME DEGRADATION; ENZYME REACTIVATION; HUMAN; HUMAN CELL; INTRACELLULAR SIGNALING; MOUSE; MYELOPROLIFERATIVE NEOPLASM; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RNA INTERFERENCE; ANIMAL; BIOSYNTHESIS; CELL LINE; DRUG ANTAGONISM; DRUG EFFECT; DRUG RESISTANCE; ENZYMOLOGY; GENE SILENCING; GENETICS; GRANULOCYTE; METABOLISM; MYELOPROLIFERATIVE DISORDER; PATHOLOGY; PHOSPHORYLATION; PROTEIN MULTIMERIZATION; PROTEIN SYNTHESIS; SIGNAL TRANSDUCTION;

MURINAE;

ANIMALS; CELL LINE; DISEASE MODELS, ANIMAL; DRUG RESISTANCE, NEOPLASM; ENZYME ACTIVATION; GENE KNOCKDOWN TECHNIQUES; GRANULOCYTES; HSP90 HEAT-SHOCK PROTEINS; HUMANS; JANUS KINASE 1; JANUS KINASE 2; MICE; MYELOPROLIFERATIVE DISORDERS; PHOSPHORYLATION; PROTEIN BIOSYNTHESIS; PROTEIN MULTIMERIZATION; RNA INTERFERENCE; SIGNAL TRANSDUCTION; STAT TRANSCRIPTION FACTORS; TYK2 KINASE;

EID: 84865735256     PISSN: 00280836     EISSN: 14764687     Source Type: Journal    
DOI: 10.1038/nature11303     Document Type: Article

References (30)

1. James, C. et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 434, 1144-1148 (2005). (Pubitemid 40663494)
2. Kralovics, R. et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N. Engl. J. Med. 352, 1779-1790 (2005). (Pubitemid 40570926)
3. Baxter, E. J. et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 365, 1054-1061 (2005). (Pubitemid 40386783)
4. Zhao, R. et al. Identification of an acquired JAK2 mutation in polycythemia vera. J. Biol. Chem. 280, 22788-22792 (2005). (Pubitemid 40853184)
5. Pikman, Y. et al.MPLW515L is a novel somatic activatingmutation inmyelofibrosis with myeloid metaplasia. PLoS Med. 3, e270 (2006).
6. Verstovsek, S. et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N. Engl. J. Med. 363, 1117-1127 (2010).
7. Pardanani, A. et al. Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis. J. Clin. Oncol. 29, 789-796 (2011).
8. Druker, B. J. et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N. Engl. J. Med. 344, 1031-1037 (2001). (Pubitemid 32267972)
9. Flaherty, K. T. et al. Inhibition ofmutated, activated BRAF in metastatic melanoma. N. Engl. J. Med. 363, 809-819 (2010).
10. Rosell, R. et al. Screening for epidermal growth factor receptor mutations in lung cancer. N. Engl. J. Med. 361, 958-967 (2009).
11. Mok, T. S. et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N. Engl. J. Med. 361, 947-957 (2009).
12. Kobayashi, S. et al. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 352, 786-792 (2005). (Pubitemid 40271173)
13. Pao, W. et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a secondmutation in the EGFR kinase domain. PLoSMed. 2, e73 (2005).
14. Gorre, M. E. et al. Clinical resistance to STI-571 cancer therapy caused byBCR-ABL gene mutation or amplification. Science 293, 876-880 (2001). (Pubitemid 32743979)
15. Engelman, J. A. et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316, 1039-1043 (2007). (Pubitemid 46799492)
16. Pao, W. et al. KRASmutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med. 2, e17 (2005).
17. Johannessen, C. M. et al. COT drives resistance to RAF inhibition through MAP kinase pathway reactivation. Nature 468, 968-972 (2010).
18. Nazarian, R. et al. Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature 468, 973-977 (2010).
19. Azam, M., Latek, R. R. & Daley, G. Q. Mechanisms of autoinhibition and STI-571/imatinib resistance revealed by mutagenesis of BCR-ABL. Cell 112, 831-843 (2003). (Pubitemid 36378885)
20. Shah, N. P. et al. Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI571) in chronic phase and blast crisis chronic myeloid leukemia. Cancer Cell 2, 117-125 (2002). (Pubitemid 41039112)
21. Sharma, S. V. et al. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell 141, 69-80 (2010).
22. Parganas, E. et al. Jak2 is essential for signaling through a variety of cytokine receptors. Cell 93, 385-395 (1998). (Pubitemid 28232083)
23. Ihle, J. N. & Gilliland, D. G. Jak2: normal function and role in hematopoietic disorders. Curr. Opin. Genet. Dev. 17, 8-14 (2007).
24. Mullighan, C. G. et al. JAK mutations in high-risk childhood acute lymphoblastic leukemia. Proc. Natl Acad. Sci. USA 106, 9414-9418 (2009).
25. Marubayashi, S. et al. HSP90 is a therapeutic target in JAK2-dependent myeloproliferative neoplasms in mice and humans. J. Clin. Invest. 120, 3578-3593 (2010).
26. Koppikar, P. et al. Efficacy of the JAK2 inhibitor INCB16562 in a murine model of MPLW515L-induced thrombocytosis and myelofibrosis. Blood 115, 2919-2927 (2010).
27. Rider, L., Shatrova, A., Feener, E. P., Webb, L. & Diakonova, M. JAK2 tyrosine kinase phosphorylates PAK1 and regulates PAK1 activity and functions. J. Biol. Chem. 282, 30985-30996 (2007). (Pubitemid 350035237)
28. Andraos, R. et al. Modulation of activation-loop phosphorylation by JAK inhibitors is binding mode dependent. Cancer Discov. 2, 512-523 (2012).
29. Wang, Y. et al. Cotreatment with panobinostat and JAK2 inhibitor TG101209 attenuates JAK2V617F levels andsignaling and exerts synergistic cytotoxic effects against human myeloproliferative neoplastic cells. Blood 114, 5024-5033 (2009).
30. Guerini, V. et al. The histone deacetylase inhibitor ITF2357 selectively targets cells bearing mutated JAK2V617F. Leukemia 22, 740-747 (2007). (Pubitemid 351552623)