Molecular pathways: Molecular basis for sensitivity and resistance to JAK kinase inhibitors

Clinical Cancer Research

Volumn 20, Issue 8, 2014, Pages 2051-2059

  Meyer, Sara C ^a   Levine, Ross L ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

JANUS KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN KINASE INHIBITOR; STAT PROTEIN;

ANTAGONISTS AND INHIBITORS; BIOLOGICAL MODEL; DRUG EFFECTS; DRUG RESISTANCE; HUMAN; METABOLISM; NEOPLASMS; SIGNAL TRANSDUCTION;

DRUG RESISTANCE, NEOPLASM; HUMANS; JANUS KINASES; MODELS, BIOLOGICAL; NEOPLASMS; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION; STAT TRANSCRIPTION FACTORS;

EID: 84898990827     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-13-0279     Document Type: Article

References (65)

1. Parganas E, Wang D, Stravopodis D, Topham DJ, Marine JC, Teglund S, et al. Jak2 is essential for signaling through a variety of cytokine receptors. Cell 1998;93:385-95.
2. Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJ, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 2005;7:387-97.
3. Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005;352:1779-90.
4. Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005;365:1054-61.
5. James C, Ugo V, Le Couedic JP, Staerk J, Delhommeau F, Lacout C, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 2005;434:1144-8.
6. Boggon TJ, Li Y, Manley PW, Eck MJ. Crystal structure of the Jak3 kinase domain in complex with a staurosporine analog. Blood 2005;106:996-1002.
7. Ungureanu D, Wu J, Pekkala T, Niranjan Y, Young C, Jensen ON, et al. The pseudokinase domain of JAK2 is a dual-specificity protein kinase that negatively regulates cytokine signaling. Nat Struct Mol Biol 2011;18:971-6.
8. Bandaranayake RM, Ungureanu D, Shan Y, Shaw DE, Silvennoinen O, Hubbard SR. Crystal structures of the JAK2 pseudokinase domain and the pathogenic mutant V617F. Nat Struct Mol Biol 2012;19:754-9.
9. Neubauer H, Cumano A, Muller M, Wu H, Huffstadt U, Pfeffer K. Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis. Cell 1998;93:397-409.
10. Lu X, Levine R, Tong W, Wernig G, Pikman Y, Zarnegar S, et al. Expression of a homodimeric type I cytokine receptor is required for JAK2V617F-mediated transformation. Proc Natl Acad Sci U S A 2005;102:18962-7.
11. Flex E, Petrangeli V, Stella L, Chiaretti S, Hornakova T, Knoops L, et al. Somatically acquired JAK1 mutations in adult acute lymphoblastic leukemia. J Exp Med 2008;205:751-8.
12. Rodig SJ, Meraz MA, White JM, Lampe PA, Riley JK, Arthur CD, et al. Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses. Cell 1998;93:373-83.
13. O'Shea JJ, Husa M, Li D, Hofmann SR, Watford W, Roberts JL, et al. Jak3 and the pathogenesis of severe combined immunodeficiency. Mol Immunol 2004;41:727-37.
14. Karaghiosoff M, Neubauer H, Lassnig C, Kovarik P, Schindler H, Pircher H, et al. Partial impairment of cytokine responses in Tyk2- deficient mice. Immunity 2000;13:549-60.
15. Roder S, Steimle C, Meinhardt G, Pahl HL. STAT3 is constitutively active in some patients with Polycythemia rubra vera. Exp Hematol 2001;29:694-702.
16. Gautier EF, Picard M, Laurent C, Marty C, Villeval JL, Demur C, et al. The cell cycle regulator CDC25A is a target for JAK2V617F oncogene. Blood 2012;119:1190-9.
17. Haan S, Wuller S, Kaczor J, Rolvering C, Nocker T, Behrmann I, et al. SOCS-mediated downregulation of mutant Jak2 (V617F, T875N and K539L) counteracts cytokine-independent signaling. Oncogene 2009; 28:3069-80.
18. Tong W, Zhang J, Lodish HF. Lnk inhibits erythropoiesis and Epodependent JAK2 activation and downstream signaling pathways. Blood 2005;105:4604-12.
19. DawsonMA, Bannister AJ, Gottgens B, Foster SD, Bartke T, Green AR, et al. JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin. Nature 2009;461:819-22.
20. Dameshek W. Some speculations on the myeloproliferative syndromes. Blood 1951;6:372-5.
21. Liu F, Zhao X, Perna F, Wang L, Koppikar P, Abdel-Wahab O, et al. JAK2V617F-mediated phosphorylation of PRMT5 downregulates its methyltransferase activity and promotes myeloproliferation. Cancer Cell 2011;19:283-94.
22. Scott LM, Scott MA, Campbell PJ, Green AR. Progenitors homozygous for the V617F mutation occur in most patients with polycythemia vera, but not essential thrombocythemia. Blood 2006; 108:2435-7.
23. Guglielmelli P, Barosi G, Specchia G, Rambaldi A, Lo Coco F, Antonioli E, et al. Identification of patients with poorer survival in primary myelofibrosis based on the burden of JAK2V617F mutated allele. Blood 2009;114:1477-83.
24. Kralovics R, Guan Y, Prchal JT. Acquired uniparental disomy of chromosome 9p is a frequent stem cell defect in polycythemia vera. Exp Hematol 2002;30:229-36.
25. Jones AV, Chase A, Silver RT, Oscier D, Zoi K, Wang YL, et al. JAK2 haplotype is a major risk factor for the development of myeloproliferative neoplasms. Nat Genet 2009;41:446-9.
26. Theocharides A, Boissinot M, Girodon F, Garand R, Teo SS, Lippert E, et al. Leukemic blasts in transformed JAK2-V617F-positive myeloproliferative disorders are frequently negative for the JAK2-V617F mutation. Blood 2007;110:375-9.
27. Scott LM, Tong W, Levine RL, Scott MA, Beer PA, Stratton MR, et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med 2007;356:459-68.
28. Pikman Y, Lee BH, Mercher T, McDowell E, Ebert BL, Gozo M, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med 2006;3:e270.
29. Tefferi A, Vaidya R, Caramazza D, Finke C, Lasho T, Pardanani A. Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primarymyelofibrosis: a comprehensive cytokine profiling study. J Clin Oncol 2011;29:1356-63.
30. Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med 2013;369:2379-90.
31. Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med 2013;369:2391-405.
32. Walz C, Ahmed W, Lazarides K, Betancur M, Patel N, Henninghausen L, et al. Essential role for Stat5a/b in myeloproliferative neoplasms induced by BCR-ABL1 and JAK2(V617F) in mice. Blood 2012;119: 3550-60.
33. Schwaller J, Parganas E, Wang D, Cain D, Aster JC, Williams IR, et al. Stat5 is essential for the myelo- and lymphoproliferative disease induced by TEL/JAK2. Mol Cell 2000;6:693-704.
34. Kamishimoto J, Tago K, Kasahara T, Funakoshi-Tago M. Akt activation through the phosphorylation of erythropoietin receptor at tyrosine 479 is required for myeloproliferative disorder-associated JAK2 V617F mutant-induced cellular transformation. Cell Signal 2011;23:849-56.
35. Levine RL, Loriaux M, Huntly BJ, Loh ML, Beran M, Stoffregen E, et al. The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia. Blood 2005;106: 3377-9.
36. Sulong S, Case M, Minto L, Wilkins B, Hall A, Irving J. The V617F mutation in Jak2 is not found in childhood acute lymphoblastic leukaemia. Br J Haematol 2005;130:964-5.
37. Kratz CP, Boll S, Kontny U, Schrappe M, Niemeyer CM, Stanulla M. Mutational screen reveals a novel JAK2 mutation, L611S, in a child with acute lymphoblastic leukemia. Leukemia 2006;20:381-3.
38. Mercher T, Wernig G, Moore SA, Levine RL, Gu TL, Frohling S, et al. JAK2T875N is a novel activating mutation that results in myeloproliferative disease with features of megakaryoblastic leukemia in a murine bone marrow transplantation model. Blood 2006;108: 2770-9.
39. Mullighan CG, Zhang J, Harvey RC, Collins-Underwood JR, Schulman BA, Phillips LA, et al. JAK mutations in high-risk childhood acute lymphoblastic leukemia. Proc Natl Acad Sci U S A 2009;106:9414-8.
40. Roberts KG, Morin RD, Zhang J, Hirst M, Zhao Y, Su X, et al. Genetic alterations activating kinase and cytokine receptor signaling in highrisk acute lymphoblastic leukemia. Cancer Cell 2012;22:153-66.
41. Lacronique V, Boureux A, Valle VD, Poirel H, Quang CT, Mauchauffe M, et al. A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia. Science 1997;278:1309-12.
42. Reiter A, Walz C, Watmore A, Schoch C, Blau I, Schlegelberger B, et al. The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2. Cancer Res 2005;65:2662-7.
43. Joos S, Kupper M, Ohl S, von Bonin F, Mechtersheimer G, Bentz M, et al. Genomic imbalances including amplification of the tyrosine kinase gene JAK2 in CD30 +Hodgkin cells. Cancer Res 2000;60: 549-52.
44. Walters DK, Mercher T, Gu TL, O'Hare T, Tyner JW, Loriaux M, et al. Activating alleles of JAK3 in acute megakaryoblastic leukemia. Cancer Cell 2006;10:65-75.
45. Koo GC, Tan SY, Tang T, Poon SL, Allen GE, Tan L, et al. Janus kinase 3-activating mutations identified in natural killer/T-cell lymphoma. Cancer Discov 2012;2:591-7.
46. Weniger MA, Melzner I, Menz CK, Wegener S, Bucur AJ, Dorsch K, et al. Mutations of the tumor suppressor gene SOCS-1 in classical Hodgkin lymphoma are frequent and associated with nuclear phospho- STAT5 accumulation. Oncogene 2006;25:2679-84.
47. Koskela HL, Eldfors S, Ellonen P, van Adrichem AJ, Kuusanmaki H, Andersson EI, et al. Somatic STAT3 mutations in large granular lymphocytic leukemia. N Engl J Med 2012;366:1905-13.
48. Liang K, Esteva FJ, Albarracin C, Stemke-Hale K, Lu Y, Bianchini G, et al. Recombinant human erythropoietin antagonizes trastuzumab treatment of breast cancer cells via Jak2-mediated Src activation and PTEN inactivation. Cancer Cell 2010;18:423-35.
49. Ding L, Xu Y, Zhang W, Deng Y, Si M, Du Y, et al. MiR-375 frequently downregulated in gastric cancer inhibits cell proliferation by targeting JAK2. Cell Res 2010;20:784-93.
50. Andraos R, Qian Z, Bonenfant D, Rubert J, Vangrevelinghe E, Scheufler C, et al. Modulation of activation-loop phosphorylation by JAK inhibitors is binding mode dependent. Cancer Discov 2012; 2:512-23.
51. Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 2012;366:799-807.
52. Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 2012;366:787-98.
53. Pardanani A, Gotlib JR, Jamieson C, Cortes JE, Talpaz M, Stone RM, et al. Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis. J Clin Oncol 2011;29:789-96.
54. Pardanani A, Laborde RR, Lasho TL, Finke C, Begna K, Al-Kali A, et al. Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis. Leukemia 2013;27:1322-7.
55. Verstovsek S, Odenike O, Scott B, Estrov Z, Cortes J, Thomas DA, et al. Phase I dose-escalation trial of SB1518, a novel JAK2/FLT3 inhibitor, in acute and chronic myeloid diseases, including primary or post-essential thrombocythemia/polycythemia vera myelofibrosis. Blood 2009; 1140:3905.
56. Fridman JS, Scherle PA, Collins R, Burn TC, Li Y, Li J, et al. Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050. J Immunol 2010;184: 5298-307.
57. Ghoreschi K, Jesson MI, Li X, Lee JL, Ghosh S, Alsup JW, et al. Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550). J Immunol 2011;186:4234-43.
58. Weigert O, Lane AA, Bird L, Kopp N, Chapuy B, van Bodegom D, et al. Genetic resistance to JAK2 enzymatic inhibitors is overcome by HSP90 inhibition. J Exp Med 2012;209:259-73.
59. Koppikar P, Bhagwat N, Kilpivaara O, Manshouri T, Adli M, Hricik T, et al. Heterodimeric JAK-STAT activation as a mechanism of persistence to JAK2 inhibitor therapy. Nature 2012;489:155-9.
60. Kalota A, Jeschke GR, Carroll M, Hexner EO. Intrinsic resistance to JAK2 inhibition in myelofibrosis. Clin Cancer Res 2013;19:1729-39.
61. Marubayashi S, Koppikar P, Taldone T, Abdel-Wahab O, West N, Bhagwat N, et al. HSP90 is a therapeutic target in JAK2-dependent myeloproliferative neoplasms in mice and humans. J Clin Invest 2010;120:3578-93.
62. DeAngelo DJ, Mesa RA, Fiskus W, Tefferi A, Paley C, WadleighM, et al. Phase II trial ofpanobinostat,anoralpan-deacetylaseinhibitor inpatients with primarymyelofibrosis, post-essential thrombocythaemia, and postpolycythaemia vera myelofibrosis. Br J Haematol 2013;162:326-35.
63. Fiskus W, Verstovsek S, Manshouri T, Smith JE, Peth K, Abhyankar S, et al. Dual PI3K/AKT/mTOR inhibitor BEZ235 synergistically enhances the activity of JAK2 inhibitor against cultured and primary human myeloproliferative neoplasm cells. Mol Cancer Ther 2013;12:577-88.
64. Suryani S, Sia KCS, Bracken L, Carol H, Evans K, Kurmasheva R, et al. Dual inhibition of JAK/STAT and MAPK pathways results in synergistic cell killing of JAK-mutated pediatric acute lymphoblastic leukemia. Blood 2012;120:3562.
65. Guglielmelli P, Barosi G, Rambaldi A, Marchioli R, Masciulli A, Biamonte F, et al. Safety and efficacy of everolimus, a mTOR inhibitor, as single agent in a phase 1/2 study in patients with myelofibrosis. Blood 2011;118:2069-76.