Preclinical and clinical activity of ATP mimetic JAK2 inhibitors

Clinical Advances in Hematology and Oncology

Volumn 8, Issue 8, 2010, Pages 557-563

  Wadleigh, Martha ^a   Tefferi, Ayalew ^b  

^a DANA FARBER CANCER INSTITUTE   (United States)

^b MAYO CLINIC   (United States)

Author keywords

Jak2 inhibitors; Myelofibrosis; Myeloproliferative neoplasms

Indexed keywords

CYT 387; INCB 018424; JANUS KINASE 2; JANUS KINASE 2 INHIBITOR; LESTAURTINIB; SB 1518; TG 101348; UNCLASSIFIED DRUG; XL 019;

ACUTE GRANULOCYTIC LEUKEMIA; AMYLASE BLOOD LEVEL; ANEMIA; ARTICLE; BALANCE DISORDER; CACHEXIA; CLINICAL TRIAL; CONFUSION; DIARRHEA; DRUG ACTIVITY; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG TOLERABILITY; ENZYME ACTIVITY; ERYTHROCYTOSIS; FORMICATION; GASTROINTESTINAL SYMPTOM; GASTROINTESTINAL TOXICITY; GENE MUTATION; HUMAN; LEUKEMIA; LEUKOCYTOSIS; MYELOFIBROSIS; MYELOID METAPLASIA; MYELOPROLIFERATIVE DISORDER; NAUSEA; NAUSEA AND VOMITING; NEUTROPENIA; NONHUMAN; OPTIMAL DRUG DOSE; PARESTHESIA; PERIPHERAL NEUROPATHY; POLYCYTHEMIA VERA; PRURITUS; RECOMMENDED DRUG DOSE; SIDE EFFECT; SOLID TUMOR; SPLENOMEGALY; THROMBOCYTHEMIA; THROMBOCYTOPENIA; THROMBOCYTOSIS; THROMBOSIS; TRIACYLGLYCEROL LIPASE BLOOD LEVEL; VOMITING;

ADENOSINE TRIPHOSPHATE; ANIMALS; CLINICAL TRIALS AS TOPIC; ENZYME INHIBITORS; HUMANS; JANUS KINASE 2; MYELOPROLIFERATIVE DISORDERS; POINT MUTATION;

EID: 77957599590     PISSN: 15430790     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (55)

1. Levine RL, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7:387-397.
2. Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365:1054-1061.
3. James C, Ugo V, Le Couedic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434:1144-1148.
4. Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352:1779-1790.
5. Zhao R, Xing S, Li Z, et al. Identification of an acquired JAK2 mutation in polycythemia vera. J Biol Chem. 2005;280:22788-22792.
6. Cools J, DeAngelo DJ, Gotlib J, et al. A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med. 2003;348:1201-1214.
7. Tefferi A, Murphy S. Current opinion in essential thrombocythemia: pathogenesis, diagnosis, and management. Blood Rev. 2001;15:121-131.
8. Tefferi A. Myelofibrosis with myeloid metaplasia. N Engl J Med. 2000;342: 1255-1265.
9. Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood. 2009;113:2895-2901.
10. Prchal JF, Axelrad AA. Letter: Bone-marrow responses in polycythemia vera. N Engl J Med. 1974;290:1382.
11. Lutton JD, Levere RD. Endogenous erythroid colony formation by peripheral blood mononuclear cells from patients with myelofibrosis and polycythemia vera. Acta Haematol. 1979;62:94-99.
12. Correa PN, Eskinazi D, Axelrad AA. Circulating erythroid progenitors in polycythemia vera are hypersensitive to insulin-like growth factor-1 in vitro: studies in an improved serum-free medium. Blood. 1994;83:99-112.
13. Dai CH, Krantz SB, Dessypris EN, Means RT Jr, Horn ST, Gilbert HS. Polycythemia vera. II. Hypersensitivity of bone marrow erythroid, granulocytemacrophage, and megakaryocyte progenitor cells to interleukin-3 and granulocytemacrophage colony-stimulating factor. Blood. 1992;80:891-899.
14. Levy DE, Darnell JE Jr. Stats: transcriptional control and biological impact. Nat Rev Mol Cell Biol. 2002;3:651-662.
15. Benekli M, Baer MR, Baumann H, Wetzler M. Signal transducer and activator of transcription proteins in leukemias. Blood. 2003;101:2940-2954.
16. Carter-Su C, Smit LS. Signaling via JAK tyrosine kinases: growth hormone receptor as a model system. Recent Prog Horm Res. 1998;53:61-82; discussion 82-83.
17. Ihle JN, Witthuhn BA, Quelle FW, Yamamoto K, Silvennoinen O. Signaling through the hematopoietic cytokine receptors. Annu Rev Immunol. 1995;13: 369-398.
18. Huang LJ, Constantinescu SN, Lodish HF. The N-terminal domain of Janus kinase 2 is required for Golgi processing and cell surface expression of erythropoietin receptor. Mol Cell. 2001;8:1327-1338.
19. Royer Y, Staerk J, Costuleanu M, Courtoy PJ, Constantinescu SN. Janus kinases affect thrombopoietin receptor cell surface localization and stability. J Biol Chem. 2005;280:27251-27261.
20. Lippert E, Boissinot M, Kralovics R, et al. The JAK2-V617F mutation is frequently present at diagnosis in patients with essential thrombocythemia and polycythemia vera. Blood. 2006;108:1865-1867.
21. Levine RL, Belisle C, Wadleigh M, et al. Clonality analysis and quantitative JAK2V617F assessment reveals an association between clonality and JAK2V617F in PV but not ET/MMM and identifies JAK2V617F negative ET and MMM patients with clonal hematopoiesis. Blood. 2006;107:4139-4141.
22. Jamieson CH, Gotlib J, Durocher JA, et al. The JAK2 V617F mutation occurs in hematopoietic stem cells in polycythemia vera and predisposes toward erythroid differentiation. Proc Natl Acad Sci U S A. 2006;103:6224-6229.
23. Lacout C, Pisani DF, Tulliez M, Gachelin FM, Vainchenker W, Villeval JL. JAK2V617F expression in murine hematopoietic cells leads to MPD mimicking human PV with secondary myelofibrosis. Blood. 2006;108:1652-1660.
24. Wernig G, Mercher T, Okabe R, Levine RL, Lee BH, Gilliland DG. Expression of Jak2V617F causes a polycythemia vera-like disease with associated myelofibrosis in a murine bone marrow transplant model. Blood. 2006;107:4274-4281.
25. Zaleskas VM, Krause DS, Lazarides K, et al. Molecular pathogenesis and therapy of polycythemia induced in mice by JAK2 V617F. PLoS One. 2006;1:e18.
26. Bumm TG, Elsea C, Corbin AS, et al. Characterization of murine JAK2V617Fpositive myeloproliferative disease. Cancer Res. 2006;66:11156-11165.
27. Beer PA, Campbell PJ, Scott LM, et al. MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort. Blood. 2008;112:141-149.
28. Pardanani AD, Levine RL, Lasho T, et al. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood. 2006; 108:3472-3476.
29. Pikman Y, Lee BH, Mercher T, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med. 2006;3:e270.
30. Scott LM, Tong W, Levine RL, et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med. 2007;356:459-468.
31. Pardanani A, Hood J, Lasho T, et al. TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations. Leukemia. 2007;21:1658-1668.
32. Verstovsek S, Kantarjian H, Pardanani A, et al. INCB018424, an oral, selective JAK2 inhibitor, shows significant clinical activity in a phase I/II study in patients with primary myelofibrosis (PMF) and post polycythemia vera/essential thrombocythemia myelofibrosis (post-PV/ET MF). Blood (ASH Annual Meeting Abstracts). 2007;110:Abstract 558.
33. Fridman J, Nussenzveig R, Liu P, et al. Discovery and preclinical characterization of INCB018424, a selective JAK2 inhibitor for the treatment of myeloproliferative disorders. Blood (ASH Annual Meeting Abstracts). 2007; 110:Abstract 3538.
34. Verstovsek S, Kantarjian HM, Pardanani AD, et al. The JAK inhibitor, INCB018424, demonstrates durable and marked clinical responses in primary myelofibrosis (PMF) and post-polycythemia/essential thrombocythemia myelofibrosis (Post PV/ET MF). Blood (ASH Annual Meeting Abstracts). 2008;112:Abstract 1762.
35. Verstovsek S, Kantarjian H, Mesa RA, et al. Long-term follow up and optimized dosing regimen of incb 018424 in patients with myelofibrosis: durable clinical, functional and symptomatic responses with improved hematological safety. Blood (ASH Annual Meeting Abstracts). 2009;114:Abstract 756.
36. Mesa RA, Verstovsek S, Kantarjian HM, et al. INCB018424, a selective JAK1/2 inhibitor, significantly improves the compromised nutritional status and frank cachexia in patients with myelofibrosis (MF). Blood (ASH Annual Meeting Abstracts). 2008;112:Abstract 1760.
37. Verstovsek S, Kantarjian HM, Pardanani AD, et al. Characterization of JAK2 V617F allele burden in advanced myelofibrosis (MF) patients: no change in V617F:WT JAK2 ratio in patients with high allele burdens despite profound clinical improvement following treatment with the JAK inhibitor, INCB018424. Blood (ASH Annual Meeting Abstracts). 2008;112:Abstract 2802.
38. Tefferi A. ASH 2009 Meeting Report-Top 10 clinically oriented abstracts in myeloproliferative neoplasms. Am J Hematol. 2010;85:190-192.
39. Wernig G, Kharas MG, Okabe R, et al. Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera. Cancer Cell. 2008;13:311-320.
40. Geron I, Abrahamsson AE, Barroga CF, et al. Selective inhibition of JAK2-driven erythroid differentiation of polycythemia vera progenitors. Cancer Cell. 2008;13:321-330.
41. Pardanani AD, Gotlib J, Jamieson C, et al. A phase I study of TG101348, an orally bioavailable JAK2-selective inhibitor, in patients with myelofibrosis. Blood (ASH Annual Meeting Abstracts). 2008;112:Abstract 97.
42. Pardanani AD, Gotlib JR, Jamieson C, et al. A phase I evaluation of TG101348, a selective JAK2 inhibitor, in myelofibrosis: clinical response is accompanied by significant reduction in JAK2V617F allele burden. Blood (ASH Annual Meeting Abstracts). 2009;114:Abstract 755.
43. Verstovsek S, Pardanani AD, Shah NP, et al. A phase I study of XL019, a selective JAK2 inhibitor, in patients with primary myelofibrosis and post-polycythemia vera/essential thrombocythemia myelofibrosis. Blood (ASH Annual Meeting Abstracts). 2007;110:Abstract 553.
44. Shah NP, Olszynski P, Sokol L, et al. A phase I study of XL019, a selective JAK2 inhibitor, in patients with primary myelofibrosis, post-polycythemia vera, or post-essential thrombocythemia myelofibrosis. Blood (ASH Annual Meeting Abstracts). 2008;112:Abstract 98.
45. Hexner EO, Serdikoff C, Jan M, et al. Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with myeloproliferative disorders. Blood. 2008;111:5663-5671.
46. Hexner E, Goldberg JD, Prchal JT, et al. A multicenter, open label phase I/II study of CEP701 (lestaurtinib) in adults with myelofibrosis; a report on phase I: A Study of the Myeloproliferative Disorders Research Consortium (MPDRC). Blood (ASH Annual Meeting Abstracts). 2009;114:Abstract 754.
47. Santos FP, Kantarjian HM, Jain N, et al. Phase 2 study of CEP-701, an orally available JAK2 inhibitor, in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis. Blood. 2010;115:1131-1136.
48. Tefferi A, Barosi G, Mesa RA, et al. International Working Group (IWG) consensus criteria for treatment response in myelofibrosis with myeloid metaplasia, for the IWG for Myelofibrosis Research and Treatment (IWG-MRT). Blood. 2006;108:1497-1503.
49. Hart S, Goh KC, Tan YC, Chithra A, Wood J. Pharmacodynamic (PD) biomarker assay validation for SB1518, a novel oral JAK2 inhibitor in phase I clinical trials for advanced leukemias, myeloproliferative diseases and lymphoma. Blood (ASH Annual Meeting Abstracts). 2009;114:Abstract 1888.
50. Verstovsek S, Odenike O, Scott B, 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 (ASH Annual Meeting Abstracts). 2009;114:Abstract 3905.
51. Goh KC, Hart S, Tan YC, Chithra A, Ong KH, Wood J. The effects of SB1518, a novel oral JAK2 inhibitor, on ex vivo expanded PV erythroid progenitors correlate with clinical observations. Blood (ASH Annual Meeting Abstracts). 2009;114:Abstract 2913.
52. Pardanani A, Lasho T, Smith G, Burns CJ, Fantino E, Tefferi A. CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients. Leukemia. 2009;23:1441-1445.
53. Verstovsek S, Passamonti F, Rambaldi A, et al. A phase 2 study of INCB018424, an oral, selective JAK1/JAK2 inhibitor, in patients with advanced polycythemia vera (PV) and essential thrombocythemia (ET) refractory to hydroxyurea. Blood (ASH Annual Meeting Abstracts). 2009;114:Abstract 311.
54. Barosi G, Birgegard G, Finazzi G, et al. Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference. Blood. 2009;113:4829-4833.
55. Moliterno AR, Hexner E, Roboz GJ, et al. An open-label study of CEP-701 in patients with JAK2 V617F-positive PV and ET: update of 39 enrolled patients. Blood (ASH Annual Meeting Abstracts). 2009;114:Abstract 753.