Comprehensive review of JAK inhibitors in myeloproliferative neoplasms

Therapeutic Advances in Hematology

Volumn 4, Issue 1, 2013, Pages 15-35

  Sonbol, Mohamad Bassam ^a   Zarzour, Ahmad ^a   Morad, Mohammad ^a   Firwana, Belal ^b   Rana, Vishal ^c   Tiu, Ramon V ^d  

^a DAMASCUS UNIVERSITY   (Syrian Arab Republic)

^b University of Missouri   (United States)

^c MAYO CLINIC   (United States)

^d TAUSSIG CANCER INSTITUTE   (United States)

Author keywords

essential thrombocythemia; Janus kinase 2; polycythemia vera; primary myelofibrosis

Indexed keywords

5 CHLORO N2 [1 (5 FLUORO 2 PYRIMIDINYL)ETHYL] N4 (5 METHYL 1H PYRAZOL 3 YL) 2,4 PYRIMIDINEDIAMINE; ANDROGEN; ANTIANEMIC AGENT; ANTINEOPLASTIC AGENT; BARICITINIB; BCR ABL PROTEIN; DANAZOL; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; HYDROXYUREA; INCB 16562; JANUS KINASE 1; JANUS KINASE 2; JANUS KINASE 3; JANUS KINASE INHIBITOR; LENALIDOMIDE; LESTAURTINIB; LNK PROTEIN; MOMELOTINIB; N TERT BUTYL 3 [5 METHYL 2 [4 [2 (1 PYRROLIDINYL)ETHOXY]PHENYLAMINO] 4 PYRIMIDINYLAMINO]BENZENESULFONAMIDE; NVP BSK805; PACRITINIB; PEGINTERFERON; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; PROTEIN; PROTEIN KINASE TYK2; RUXOLITINIB; THALIDOMIDE; THROMBOPOIETIN RECEPTOR; TOFACITINIB; UNCLASSIFIED DRUG; XL 019;

ABDOMINAL PAIN; ANEMIA; ANOREXIA; ASTHENIA; AUTOIMMUNE DISEASE; BONE MARROW SUPPRESSION; BONE MARROW TRANSPLANTATION; CANCER PROGNOSIS; CHRONIC MYELOMONOCYTIC LEUKEMIA; COUGHING; DEEP VEIN THROMBOSIS; DIARRHEA; DIZZINESS; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ERUPTION; DRUG HYPERSENSITIVITY; DRUG SAFETY; DRUG TARGETING; DRUG WITHDRAWAL; DYSGEUSIA; EXON; FATIGUE; FLUSHING; GAIN OF FUNCTION MUTATION; GASTROINTESTINAL HEMORRHAGE; GASTROINTESTINAL SYMPTOM; GASTROINTESTINAL TOXICITY; GENE DELETION; GENE MUTATION; GLIOBLASTOMA; HEART ATRIUM FLUTTER; HEMATOMA; HODGKIN DISEASE; HUMAN; HYPOTENSION; INTERNATIONAL PROGNOSTIC SCORING SYSTEM; KIDNEY TUMOR; LEG CRAMP; LOEFFLER PNEUMONIA; LUNG EMBOLISM; LYMPHOMA; MAST CELL LEUKEMIA; MULTIPLE CYCLE TREATMENT; MYELOFIBROSIS; MYELOID METAPLASIA; MYELOPROLIFERATIVE NEOPLASM; NAUSEA; NEUROTOXICITY; NEUTROPENIA; NEUTROPHIL COUNT; NIGHT SWEAT; NONHUMAN; PATHOGENESIS; PERIPHERAL EDEMA; PERIPHERAL NEUROPATHY; PHASE 3 CLINICAL TRIAL (TOPIC); PHLEBOTOMY; POLYCYTHEMIA VERA; PORTAL VEIN THROMBOSIS; PRIORITY JOURNAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RHEUMATOID ARTHRITIS; SEPSIS; SIDE EFFECT; SIGNAL TRANSDUCTION; SOLID TUMOR; SOMATIC MUTATION; SPLEEN; THROMBOCYTE COUNT; THROMBOCYTOPENIA; TUMOR SUPPRESSOR GENE; UNIPARENTAL DISOMY; VIRUS INFECTION; VOMITING; WILD TYPE;

EID: 84993710537     PISSN: 20406207     EISSN: 20406215     Source Type: Journal    
DOI: 10.1177/2040620712461047     Document Type: Article

References (93)

1. Baffert F. Regnier C. de Pover A. Pissot-Soldermann C. Tavares G. Blasco F. et al. (2010) Potent and selective inhibition of polycythemia by the quinoxaline JAK2 inhibitor NVP-BSK805. Mol Cancer Ther 9: 1945–1955.
2. Bartram C. de Klein A. Hagemeijer A. van Agthoven T. Geurts van Kessel A. Bootsma D. et al. (1983) Translocation of C-Ab1 oncogene correlates with the presence of a Philadelphia chromosome in chronic myelocytic leukaemia. Nature 306: 277–280.
3. Baxter E. Scott L. Campbell P. East C. Fourouclas N. Swanton S. et al. (2005) Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 365: 1054–1061.
4. Beer P. Campbell P. Scott L. Bench A. Erber W. Bareford D. et al. (2008) MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort. Blood 112: 141–149.
5. Bumm T. Tyner J. Deininger J. Loriaux M. Vandyke J. Druker B. et al. (2008) Effects of CYT387, a potent novel JAK2 inhibitor on JAK2-V617F induced MPD [abstract]. ASH Annual Meeting Abstracts 112: 856.
6. Carroll M. Tomasson M. Barker G. Golub T. Gilliland D. (1996) The TEL/platelet-derived growth factor beta receptor (PDGF Beta R) fusion in chronic myelomonocytic leukemia is a transforming protein that self-associates and activates PDGF Beta R kinase-dependent signaling pathways. Proc Natl Acad Sci U S A 93: 14845–14850.
7. Chen J. Deangelo D. Kutok J. Williams I. Lee B. Wadleigh M. et al. (2004) PKC 412 inhibits the zinc finger 198-fibroblast growth factor receptor 1 fusion tyrosine kinase and is active in treatment of stem cell myeloproliferative disorder. Proc Natl Acad Sci U S A 101: 14479–14484.
8. Cools J. Deangelo D. Gotlib J. Stover E. Legare R. Cortes J. et al. (2003) 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 348: 1201–1214.
9. Dameshek W. (1951) Some speculations on the myeloproliferative syndromes. Blood 6: 372–375.
10. Dawson M. Bannister A. Gottgens B. Foster S. Bartke T. Green A. et al. (2009) JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin. Nature 461: 819–822.
11. Deeg H. Odenike O. Scott B. Estrov Z. Cortes J. Thomas D. et al. (2011) Phase II study of SB1518, an orally available novel JAK2 inhibitor, in patients with myelofibrosis J Clin Oncol 29: Abstract 6515.
12. Fridman J. Scherle P. Collins R. Burn T. Neilan C. Hertel D. et al. (2011) Preclinical evaluation of local JAK1 and JAK2 inhibition in cutaneous inflammation. J Invest Dermatol 131: 1838–1844.
13. Gangat N. Caramazza D. Vaidya R. George G. Begna K. Schwager S. et al. (2011) DIPSS Plus: a refined dynamic international prognostic scoring system for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol 29: 392–397.
14. Garcon L. Rivat C. James C. Lacout C. Camara-Clayette V. Ugo V. et al. (2006) Constitutive activation of STAT 5 and BCL-XL overexpression can induce endogenous erythroid colony formation in human primary cells. Blood 108: 1551–1554.
15. Golub T. Barker G. Lovett M. Gilliland D. (1994) Fusion of PDGF receptor Beta to a novel ETS-like gene, TEL, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation. Cell 77: 307–316.
16. Guglielmelli P. Pancrazzi A. Bergamaschi G. Rosti V. Villani L. Antonioli E. et al. (2007) Anaemia characterises patients with myelofibrosis harbouring MPL mutation. Br J Haematol 137: 244–247.
17. Guschin D. Rogers N. Briscoe J. Witthuhn B. Watling D. Horn F. et al. (1995) A major role for the protein tyrosine kinase JAK1 in the JAK / STAT signal transduction pathway in response to interleukin-6. EMBO J 14: 1421–1429.
18. Harrison C. Kiladjian J. Al-Ali H. Gisslinger H. Waltzman R. Stalbovskaya V. et al. (2012) JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 366: 787–798.
19. Harrison C. Kiladjian J. Al-Ali H. Gisslinger H. Waltzman R. Stalbovskaya V. et al. (2011) Results of a randomized study of the JAK inhibitor ruxolitinib (INC424) versus best available therapy (BAT) in primary myelofibrosis, postpolycythemia vera-myelofibrosis (PPV-MF), or postessential thrombocythemia-myelofibrosis (PET-MF) J Clin Oncol 29 (Suppl): Abstract LBA6501.
20. Hedvat M. Huszar D. Herrmann A. Gozgit J. Schroeder A. Sheehy A. et al. (2009) The JAK2 inhibitor AZD 1480 potently blocks STAT 3 signaling and oncogenesis in solid tumors. Cancer Cell 16: 487–497.
21. Hexner E. Serdikoff C. Jan M. Swider C. Robinson C. Yang S. et al. (2008) Lestaurtinib (CEP701) is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with myeloproliferative disorders. Blood 111: 5663–5671.
22. Ihle J. Witthuhn B. Quelle F. Yamamoto K. Silvennoinen O. (1995) Signaling through the hematopoietic cytokine receptors. Annu Rev Immunol 13: 369–398.
23. Ioannidis S. Lamb M. Wang T. Almeida L. Block M. Davies A. et al. (2011) Discovery of 5-chloro-N2-[(1S)-1-(5-fluoropyrimidin-2-Yl)ethyl]-N4-(5-methyl-1H-pyrazol -3-Yl)pyrimidine-2,4-diamine (AZD1480) as a novel inhibitor of the JAK / STAT pathway. J Med Chem 54: 262–276.
24. James C. Ugo V. Le Couedic J. Staerk J. Delhommeau F. Lacout C. et al. (2005) A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 434: 1144–1148.
25. Komrokji R. Wadleigh M. Seymour J. Roberts A. To L. Zhu H. et al. (2011) Results of a phase 2 study of pacritinib (SB1518), a novel oral JAK2 inhibitor, in patients with primary, post-polycythemia vera, and post-essential thrombocythemia myelofibrosis [abstract]. ASH Annual Meeting Abstracts 118: 282.
26. Koppikar P. Abdel-Wahab O. Hedvat C. Marubayashi S. Patel J. Goel A. et al. (2010) Efficacy of the JAK2 inhibitor INCB 16562 in a murine model of MPLW515L-induced thrombocytosis and myelofibrosis. Blood 115: 2919–2927.
27. Kralovics R. Passamonti F. Buser A. Teo S. Tiedt R. Passweg J. et al. (2005) A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 352: 1779–1790.
28. Kumar C. Purandare A. Lee F. Lorenzi M. (2009) Kinase drug discovery approaches in chronic myeloproliferative disorders. Oncogene 28: 2305–2313.
29. Lacout C. Pisani D. Tulliez M. Gachelin F. Vainchenker W. Villeval J. (2006) JAK2V617F expression in murine hematopoietic cells leads to MPD mimicking human PV with secondary myelofibrosis. Blood 108: 1652–1660.
30. Lasho T. Pardanani A. Tefferi A. (2010) LNK mutations in JAK2 mutation-negative erythrocytosis. N Engl J Med 363: 1189–1190.
31. Levine R. Wadleigh M. Cools J. Ebert B. Wernig G. Huntly B. et al. (2005) Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 7: 387–397.
32. Levis M. Tse K. Smith B. Garrett E. Small D. (2001) A FLT 3 tyrosine kinase inhibitor is selectively cytotoxic to acute myeloid leukemia blasts harboring FLT 3 internal tandem duplication mutations. Blood 98: 885–887.
33. Li J. Favata M. Kelley J. Caulder E. Thomas B. Wen X. et al. (2010) INCB16562, a JAK1/2 selective inhibitor, is efficacious against multiple myeloma cells and reverses the protective effects of cytokine and stromal cell support. Neoplasia 12: 28–38.
34. Liu P. Caulder E. Li J. Waeltz P. Margulis A. Wynn R. et al. (2009) Combined inhibition of Janus kinase 1 / 2 for the treatment of JAK2V617F-driven neoplasms: selective effects on mutant cells and improvements in measures of disease severity. Clin Cancer Res 15: 6891–6900.
35. Manshouri T. Quintas-Cardama A. Nussenzveig R. Gaikwad A. Estrov Z. Prchal J. et al. (2008) The JAK kinase inhibitor CP-690,550 suppresses the growth of human polycythemia vera cells carrying the JAK2V617F mutation. Cancer Sci 99: 1265–1273.
36. Marshall J. Kindler H. Deeken J. Bhargava P. Vogelzang N. Rizvi N. et al. (2005) Phase I trial of orally administered CEP-701, a novel neurotrophin receptor-linked tyrosine kinase inhibitor. Invest New Drugs 23: 31–37.
37. McLornan D.P. Mead A.J. Jackson G. Harrison C.N. (2012) Allogeneic stem cell transplantation for myelofibrosis in 2012. Br J Haematol 157 (4): 413–25.
38. Moliterno A. Hexner E. Roboz G. Carroll M. Luger S. Mascarenhas J. et al. (2009) An open-label study of CEP-701 in patients with JAK2V617F-positive PV and ET: update of 39 enrolled patients [abstract]. ASH Annual Meeting Abstracts 114: 753.
39. Nagata H. Worobec A. Oh C. Chowdhury B. Tannenbaum S. Suzuki Y. et al. (1995) Identification of a point mutation in the catalytic domain of the protooncogene c-Kit in peripheral blood mononuclear cells of patients who have mastocytosis with an associated hematologic disorder. Proc Natl Acad Sci U S A 92: 10560–10564.
40. Nosaka T. van Deursen J. Tripp R. Thierfelder W. Witthuhn B. McMickle A. et al. (1995) Defective lymphoid development in mice lacking JAK3. Science 270: 800–802.
41. O'Shea J. Pesu M. Borie D. Changelian P. (2004) A new modality for immunosuppression: targeting the JAK / STAT pathway. Nat Rev Drug Discov 3: 555–564.
42. Oh S. Simonds E. Jones C. Hale M. Goltsev Y. Gibbs K. et al. (2010) Novel mutations in the inhibitory adaptor protein LNK drive JAK-STAT signaling in patients with myeloproliferative neoplasms. Blood 116: 988–992.
43. Panteli K. Hatzimichael E. Bouranta P. Katsaraki A. Seferiadis K. Stebbing J. et al. (2005) Serum interleukin (IL)-1, IL-2, SIL-2RA, IL-6 and thrombopoietin levels in patients with chronic myeloproliferative diseases. Br J Haematol 130: 709–715.
44. Paquette R. Sokol L. Shah N. Silver R. List A. Clary D. et al. (2008) A phase I study of XL019, a selective JAK2 inhibitor, in patients with polycythemia vera [abstract]. ASH Annual Meeting Abstracts 112: 2810.
45. Pardanani A. Caramazza D. George G. Lasho T. Hogan W. Litzow M. et al. (2011 a) Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor for the treatment of myelofibrosis. In 2011 American Society of Hematology (ASH) Annual Meeting, Poster #3849.
46. Pardanani A. Gotlib J. Jamieson C. Cortes J. Talpaz M. Stone R. et al. (2011 b) Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis. J Clin Oncol 29: 789–796.
47. Pardanani A. Lasho T. Finke C. Hanson C. Tefferi A. (2007) Prevalence and clinicopathologic correlates of JAK2 exon 12 mutations in JAK2V617F-negative polycythemia vera. Leukemia 21: 1960–1963.
48. Pardanani A. Lasho T. Finke C. Oh S. Gotlib J. Tefferi A. (2010) LNK mutation studies in blast-phase myeloproliferative neoplasms, and in chronic-phase disease with TET2, IDH, JAK2 or MPL mutations. Leukemia 24: 1713–1718.
49. Pardanani A. Lasho T. Smith G. Burns C. Fantino E. Tefferi A. (2009) 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 23: 1441–1445.
50. Pardanani A. Levine R. Lasho T. Pikman Y. Mesa R. Wadleigh M. et al. (2006) MPL 515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood 108: 3472–3476.
51. Parganas E. Wang D. Stravopodis D. Topham D. Marine J. Teglund S. et al. (1998) JAK2 is essential for signaling through a variety of cytokine receptors. Cell 93: 385–395.
52. Passamonti F. Elena C. Schnittger S. Skoda R. Green A. Girodon F. et al. (2011) Molecular and clinical features of the myeloproliferative neoplasm associated with JAK2 exon 12 mutations. Blood 117: 2813–2816.
53. Passamonti F. Rumi E. Pietra D. Elena C. Boveri E. Arcaini L. et al. (2010) A prospective study of 338 patients with polycythemia vera: the impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications. Leukemia 24: 1574–1579.
54. Pesu M. Laurence A. Kishore N. Zwillich S. Chan G. O'Shea J. (2008) Therapeutic targeting of Janus kinases. Immunol Rev 223: 132–142.
55. Pikman Y. Lee B. Mercher T. McDowell E. Ebert B. Gozo M. et al. (2006) MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med 3: e270.
56. Quintas-Cardama A. Kantarjian H. Cortes J. Verstovsek S. (2011) Janus kinase inhibitors for the treatment of myeloproliferative neoplasias and beyond. Nat Rev Drug Discov 10: 127–140.
57. Santos F. Kantarjian H. Jain N. Manshouri T. Thomas D. Garcia-Manero G. et al. (2010) Phase 2 study of CEP-701, an orally available JAK2 inhibitor, in patients with primary or post-polycythemia vera / essential thrombocythemia myelofibrosis. Blood 115: 1131–1136.
58. Schmitt A. Jouault H. Guichard J. Wendling F. Drouin A. Cramer E. (2000) Pathologic interaction between megakaryocytes and polymorphonuclear leukocytes in myelofibrosis. Blood 96: 1342–1347.
59. Scott L. Tong W. Levine R. Scott M. Beer P. Stratton M. et al. (2007) JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med 356: 459–468.
60. Scuto A. Krejci P. Popplewell L. Wu J. Wang Y. Kujawski M. et al. (2011) The novel JAK inhibitor AZD 1480 blocks STAT 3 and FGFR 3 signaling, resulting in suppression of human myeloma cell growth and survival. Leukemia 25: 538–550.
61. Seymour F. To B. Goh A. Meadows L. Ethirajulu A. Wood A. et al. (2010) First report of the phase-I study of the novel oral JAK2 inhibitor SB 1518 in patients with myelofibrosis Haematologica 95 (Suppl. 2): Abstract 1144.
62. Shah N. Olszynski P. Sokol L. Verstovsek S. Hoffman R. List A. et al. (2008) A phase I study of XL019, a selective JAK2 inhibitor, in patients with primary myelofibrosis, post-polycythemia vera, or post-essential thrombocythemia myelofibrosis [abstract]. ASH Annual Meeting Abstracts 112: 98.
63. Shuai K. Liu B. (2003) Regulation of JAK-STAT signalling in the immune system. Nat Rev Immunol 3: 900–911.
64. Silver R. Vandris K. Wang Y. Adriano F. Jones A. Christos P. et al. (2011) JAK2(V617F) allele burden in polycythemia vera correlates with grade of myelofibrosis, but is not substantially affected by therapy. Leuk Res 35: 177–182.
65. Smith B. Levis M. Beran M. Giles F. Kantarjian H. Berg K. et al. (2004) Single-agent CEP-701, a novel FLT 3 inhibitor, shows biologic and clinical activity in patients with relapsed or refractory acute myeloid leukemia. Blood 103: 3669–3676.
66. Takaki S. Morita H. Tezuka Y. Takatsu K. (2002) Enhanced hematopoiesis by hematopoietic progenitor cells lacking intracellular adaptor protein, LNK. J Exp Med 195: 151–160.
67. Tefferi A. (2000) Myelofibrosis with myeloid metaplasia. N Engl J Med 342: 1255–1265.
68. Tefferi A. (2010) Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1. Leukemia 24: 1128–1138.
69. Tefferi A. (2011) Primary myelofibrosis: 2012 update on diagnosis, risk stratification, and management. Am J Hematol 86: 1017–1026.
70. Tefferi A. (2012) Polycythemia vera and essential thrombocythemia: 2012 update on diagnosis, risk stratification, and management. Am J Hematol 87: 285–293.
71. Tefferi A. Jimma T. Gangat N. Vaidya R. Begna K. Hanson C. et al. (2011) Predictors of greater than 80% 2-year mortality in primary myelofibrosis: a Mayo Clinic study of 884 karyotypically annotated patients. Blood 118: 4595–4598.
72. Tefferi A. Lasho T. Huang J. Finke C. Mesa R. Li C. et al. (2008) Low JAK2V617F allele burden in primary myelofibrosis, compared to either a higher allele burden or unmutated status, is associated with inferior overall and leukemia-free survival. Leukemia 22: 756–761.
73. Tefferi A. Vardiman J.W. (2008) Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia 22: 14–22.
74. Tong W. Lodish H. (2004) LNK inhibits TPO-MPL signaling and TPO-mediated megakaryocytopoiesis. J Exp Med 200: 569–580.
75. Tyner J. Bumm T. Deininger J. Wood L. Aichberger K. Loriaux M. et al. (2010) CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms. Blood 115: 5232–5240.
76. Vainchenker W. Dusa A. Constantinescu S. (2008) JAKs in pathology: role of Janus kinases in hematopoietic malignancies and immunodeficiencies. Semin Cell Dev Biol 19: 385–393.
77. Vannucchi A. Antonioli E. Guglielmelli P. Longo G. Pancrazzi A. Ponziani V. et al. (2007) Prospective identification of high-risk polycythemia vera patients based on JAK2(V617F) allele burden. Leukemia 21: 1952–1959.
78. Vannucchi A. Antonioli E. Guglielmelli P. Pancrazzi A. Guerini V. Barosi G. et al. (2008) Characteristics and clinical correlates of MPL 515W>L/K mutation in essential thrombocythemia. Blood 112: 844–847.
79. Velazquez L. Cheng A. Fleming H. Furlonger C. Vesely S. Bernstein A. et al. (2002) Cytokine signaling and hematopoietic homeostasis are disrupted in LNK-deficient mice. J Exp Med 195: 1599–1611.
80. Verstovsek S. (2011 a) Response: a randomized, open label, phase III study of INC 424 in polycythemia vera (PV) patients resistant to or intolerant of hydroxyurea (HU). J Clin Oncol 29: Abstract TPS203.
81. Verstovsek S. (2011 b) Study of efficacy and safety in polycythemia vera subjects who are resistant to or intolerant of hydroxyurea: JAK inhibitor INC 424 (INCB018424) tablets versus best available care: the Response trial. http://clinicaltrials.gov/ct2/show/NCT01243944.
82. Verstovsek S. Hoffman R. Ribrag V. (2011 a) Study to assess the safety of AZD 1480 in patients with myeloproliferative diseases. http://clinicaltrial.gov/ct2/show/NCT00910728.
83. Verstovsek S. Kantarjian H. Mesa R. Pardanani A. Cortes-Franco J. Thomas D. et al. (2010 a) Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med 363: 1117–1127.
84. Verstovsek S. Mesa R. Gotlib J. Levy R. Gupta V. Dipersio J. et al. (2012) A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 366: 799–807.
85. Verstovsek S. Mesa R. Gotlib J. Levy R. Gupta V. Dipersio J. et al. (2011 b) Results of COMFORT-1, a randomized double-blind phase III trial of INCB 18424 versus placebo for patients with myelofibrosis. J Clin Oncol 29 (Suppl): Abstract 6500.
86. Verstovsek S. Odenike O. Scott B. Estrov Z. Cortes J. Thomas D. et al. (2009) 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 114: Abstract 3905.
87. Verstovsek S. Passamonti F. Rambaldi A. Barosi G. Rosen P. Levy R. et al. (2010 b) Durable responses with the JAK1/ JAK2 inhibitor, INCB018424, in patients with polycythemia vera (PV) and essential thrombocythemia (ET) refractory or intolerant to hydroxyurea (HU) [abstract]. ASH Annual Meeting Abstracts 116: 313.
88. Wang J. Chang T. Goldberg A. Novetsky A. Lichter S. Lipton J. (2006) Quantitative analysis of growth factor production in the mechanism of fibrosis in agnogenic myeloid metaplasia. Exp Hematol 34: 1617–1623.
89. Wernig G. Kharas M. Okabe R. Moore S. Leeman D. Cullen D. et al. (2008) Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera. Cancer Cell 13: 311–320.
90. Wernig G. Mercher T. Okabe R. Levine R. Lee B. Gilliland D. (2006) Expression of JAK2V617F causes a polycythemia vera-like disease with associated myelofibrosis in a murine bone marrow transplant model. Blood 107: 4274–4281.
91. Xiao S. Nalabolu S. Aster J. Ma J. Abruzzo L. Jaffe E. et al. (1998) FGFR 1 is fused with a novel zinc-finger gene, ZnF198, in the t(8;13) leukaemia / lymphoma syndrome. Nat Genet 18: 84–87.
92. Xin H. Herrmann A. Reckamp K. Zhang W. Pal S. Hedvat M. et al. (2011) Antiangiogenic and antimetastatic activity of JAK inhibitor AZD1480. Cancer Res 71: 6601–6610.
93. Xu M. Bruno E. Chao J. Huang S. Finazzi G. Fruchtman S. et al. (2005) Constitutive mobilization of CD34+ cells into the peripheral blood in idiopathic myelofibrosis may be due to the action of a number of proteases. Blood 105: 4508–4515.