Janus kinase Inhibition and its effect upon the therapeutic landscape for myelofibrosis: From palliation to cure?

British Journal of Haematology

Volumn 157, Issue 4, 2012, Pages 426-437

  Harrison, Claire ^a   Verstovsek, Srdan ^b   Mcmullin, Mary F ^c   Mesa, Ruben ^d  

^a GUY'S AND ST THOMAS' NHS FOUNDATION TRUST   (United Kingdom)

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

^c QUEEN'S UNIVERSITY BELFAST   (United Kingdom)

^d MAYO CLINIC   (United States)

Author keywords

Janus kinase 2; Janus kinase inhibitors; Myelofibrosis; Myeloproliferative neoplasms

Indexed keywords

ACETYLSALICYLIC ACID; ANAGRELIDE; ANTIANEMIC AGENT; CLADRIBINE; CORTICOSTEROID; CYT 387; DANAZOL; HYDROXYUREA; INCB 028050; INCB 16562; INTERFERON; JANUS KINASE; JANUS KINASE 1; JANUS KINASE 2; JANUS KINASE 2 INHIBITOR; JANUS KINASE INHIBITOR; LENALIDOMIDE; LESTAURTINIB; LY 2784544; NVP BSK 805; PACRITINIB; PLACEBO; POMALIDOMIDE; R 723; RUXOLITINIB; SAR 302503; SB 1518; TG 101348; THALIDOMIDE; UNCLASSIFIED DRUG; XL 019;

ACUTE GRANULOCYTIC LEUKEMIA; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; ANEMIA; ANXIETY DISORDER; ASTHENIA; CHRONIC MYELOID LEUKEMIA; CLINICAL EFFECTIVENESS; DIARRHEA; DIZZINESS; DOSE RESPONSE; DRUG DOSE TITRATION; DRUG EFFECT; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; ECCHYMOSIS; ENZYME INHIBITION; FATIGUE; FEVER; GASTROINTESTINAL TOXICITY; GENE; GENE MUTATION; HEADACHE; HUMAN; HYPERAMYLASEMIA; INSOMNIA; JANUS KINASE 2 GENE; LOW DRUG DOSE; MULTIPLE CYCLE TREATMENT; MYELOFIBROSIS; MYELOID METAPLASIA; NEUTROPENIA; NONHUMAN; OUTCOME ASSESSMENT; PALLIATIVE THERAPY; PERIPHERAL EDEMA; PHLEBOTOMY; POLYCYTHEMIA VERA; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; SPLENECTOMY; SPLENOMEGALY; SYSTEMIC INFLAMMATORY RESPONSE SYNDROME; THROMBOCYTHEMIA; THROMBOCYTOPENIA; THROMBOSIS; TREATMENT DURATION;

ANTINEOPLASTIC AGENTS; HUMANS; JANUS KINASE 2; JANUS KINASES; MUTATION; MYELOPROLIFERATIVE DISORDERS; PALLIATIVE CARE; PRIMARY MYELOFIBROSIS; PROTEIN KINASE INHIBITORS;

EID: 84860010662     PISSN: 00071048     EISSN: 13652141     Source Type: Journal    
DOI: 10.1111/j.1365-2141.2012.09108.x     Document Type: Review

References (65)

1. Aaronson, N.K., Ahmedzai, S., Bergman, B., Bullinger, M., Cull, A., Duez, N.J., Filiberti, A., Flechtner, H., Fleishman, S.B., de Haes, J.C., Kaasa, S., Klee, M., Osoba, D., Razavi, D., Rofe, P.B., Schraub, S., Sneeuw, K., Sullivan, M. & Takeda, F. (1993) The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. Journal of the National Cancer Institute, 85, 365-376.
2. Baffert, F., Regnier, C.H., De Pover, A., Pissot-Soldermann, C., Tavares, G.A., Blasco, F., Brueggen, J., Chene, P., Drueckes, P., Erdmann, D., Furet, P., Gerspacher, M., Lang, M., Ledieu, D., Nolan, L., Ruetz, S., Trappe, J., Vangrevelinghe, E., Wartmann, M., Wyder, L., Hofmann, F. & Radimerski, T. (2010) Potent and Selective Inhibition of Polycythemia by the Quinoxaline JAK2 Inhibitor NVP-BSK805. Molecular Cancer Therapeutics, 9, 1945-1955.
3. Barbui, T., Barosi, G., Birgegard, G., Cervantes, F., Finazzi, G., Griesshammer, M., Harrison, C., Hasselbalch, H.C., Hehlmann, R., Hoffman, R., Kiladjian, J.J., Kroger, N., Mesa, R., McMullin, M.F., Pardanani, A., Passamonti, F., Vannucchi, A.M., Reiter, A., Silver, R.T., Verstovsek, S. & Tefferi, A. (2011) Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. Journal of Clinical Oncology, 29, 761-770.
4. Barosi, G., Birgegard, G., Finazzi, G., Griesshammer, M., Harrison, C., Hasselbalch, H.C., Kiladjian, J.J., Lengfelder, E., McMullin, M.F., Passamonti, F., Reilly, J.T., Vannucchi, A.M. & Barbui, T. (2009) Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference. Blood, 113, 4829-4833.
5. Baxter, E.J., Scott, L.M., Campbell, P.J., East, C., Fourouclas, N., Swanton, S., Vassiliou, G.S., Bench, A.J., Boyd, E.M., Curtin, N., Scott, M.A., Erber, W.N. & Green, A.R. (2005) Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet, 365, 1054-1061.
6. Brucker, P.S., Yost, K., Cashy, J., Webster, K. & Cella, D. (2005) General population and cancer patient norms for the Functional Assessment of Cancer Therapy-General (FACT-G). Evaluation and the Health Professions, 28, 192-211.
7. Campbell, P.J. & Green, A.R. (2006) The myeloproliferative disorders. New England Journal of Medicine, 355, 2452-2466.
8. Cervantes, F., Dupriez, B., Pereira, A., Passamonti, F., Reilly, J.T., Morra, E., Vannucchi, A.M., Mesa, R.A., Demory, J.L., Barosi, G., Rumi, E. & Tefferi, A. (2009) New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood, 113, 2895-2901.
9. Fridman, J., Nussenzveig, R. & Liu, P. (2007) Discovery and Preclinical Characterization of INCB018424, a Selective JAK2 Inhibitor for the Treatment of Myeloproliferative Disorders. Blood (ASH Annual Meeting Abstracts), 110, Abstract 3538.
10. Fridman, J.S., Scherle, P.A., Collins, R., Burn, T.C., Li, Y., Li, J., Covington, M.B., Thomas, B., Collier, P., Favata, M.F., Wen, X., Shi, J., McGee, R., Haley, P.J., Shepard, S., Rodgers, J.D., Yeleswaram, S., Hollis, G., Newton, R.C., Metcalf, B., Friedman, S.M. & Vaddi, K. (2010) Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050. Journal of Immunology, 184, 5298-5307.
11. Gale, R.P., Barosi, G., Barbui, T., Cervantes, F., Dohner, K., Dupriez, B., Gupta, V., Harrison, C., Hoffman, R., Kiladjian, J.J., Mesa, R., Mc Mullin, M.F., Passamonti, F., Ribrag, V., Roboz, G., Saglio, G., Vannucchi, A. & Verstovsek, S. (2011) What are RBC-transfusion-dependence and -independence? Leukemia Research, 35, 8-11.
12. Guglielmelli, P., Biamonte, F., Score, J., Hidalgo-Curtis, C., Cervantes, F., Maffioli, M., Fanelli, T., Ernst, T., Winkelmann, N., Jones, A.V., Zoi, K., Reiter, A., Duncombe, A., Villani, L., Bosi, A., Barosi, G., Cross, N.C. & Vannucchi, A.M. (2011) EZH2 mutational status predicts poor survival in myelofibrosis. Blood, 118, 5227-5234.
13. Harrison, C.N., Kiladjian, J.J., Gisslinger, H., Niederwieser, D., Passamonti, F., Waltzman, R.J., Hollaender, N., Hunter, D.S., Levy, R.S., Knoops, L., Cervantes, F., Vannucchi, A.N., Barbui, T. & Barosi, G. (2011) Ruxolitinib Provides Reductions in Splenomegaly Across Subgroups: an Analysis of Spleen Response in the COMFORT-II Study. Blood (ASH Annual Meeting Abstracts), 118, Abstract 279.
14. Harrison, C., Kiladjian, J.J., Al-Ali, H.K., Gisslinger, H., Waltzman, R., Stalbovskaya, V., McQuitty, M., Hunter, D.S., Levy, R., Knoops, L., Cervantes, F., Vannucchi, A.M., Barbui, T. & Barosi, G. (2012) JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. The New England Journal of Medicine, 366, 787-798.
15. Hart, S., Goh, K.C., Novotny-Diermayr, V., Hu, C.Y., Hentze, H., Tan, Y.C., Madan, B., Amalini, C., Loh, Y.K., Ong, L.C., William, A.D., Lee, A., Poulsen, A., Jayaraman, R., Ong, K.H., Ethirajulu, K., Dymock, B.W. & Wood, J.W. (2011) SB1518, a novel macrocyclic pyrimidine-based JAK2 inhibitor for the treatment of myeloid and lymphoid malignancies. Leukemia, 25, 1751-1759.
16. Hernandez-Boluda, J.C., Alvarez-Larran, A., Gomez, M., Angona, A., Amat, P., Bellosillo, B., Martinez-Aviles, L., Navarro, B., Teruel, A., Martinez-Ruiz, F. & Besses, C. (2011) Clinical evaluation of the European LeukaemiaNet criteria for clinicohaematological response and resistance/intolerance to hydroxycarbamide in essential thrombocythaemia. British Journal of Haematology, 152, 81-88.
17. Heuck, G. (1879) Zwei Fälle von Leukämie mit eigenthümlichem Blut-resp Knochenmarksbefund. Virchows Archiv (Pathological Anatomy), 78, 475.
18. Hexner, E.O., Serdikoff, C., Jan, M., Swider, C.R., Robinson, C., Yang, S., Angeles, T., Emerson, S.G., Carroll, M., Ruggeri, B. & Dobrzanski, P. (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.
19. Hexner, E., Goldberg, J.D., Prchal, J.T., Demakos, E.P., Swierczek, S., Weinberg, R.S., Tripodi, J., Najfeld, V., Carroll, M., Marchioli, R., Silverman, L.R. & Hoffman, R. (2009) 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. Blood (ASH Annual Meeting Abstracts), 114, Abstract 754.
20. James, C., Ugo, V., Le Couedic, J.P., Staerk, J., Delhommeau, F., Lacout, C., Garcon, L., Raslova, H., Berger, R., Bennaceur-Griscelli, A., Villeval, J.L., Constantinescu, S.N., Casadevall, N. & Vainchenker, W. (2005) A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature, 434, 1144-1148.
21. Jiang, J.K., Ghoreschi, K., Deflorian, F., Chen, Z., Perreira, M., Pesu, M., Smith, J., Nguyen, D.T., Liu, E.H., Leister, W., Costanzi, S., O'Shea, J.J. & Thomas, C.J. (2008) Examining the chirality, conformation and selective kinase inhibition of 3-((3R, 4R)-4-methyl-3-(methyl(7H-pyrrolo[2, 3-d]pyrimidin-4-yl)amino)piperi din-1-yl)-3-oxopropanenitrile (CP-690, 550). Journal of Medicinal Chemistry, 51, 8012-8018.
22. Kiladjian, J.J., Lesteven, E., Massé, A., Cassinat, B., Turlure, P., Bellucci, S. & Delhommeau, F. (2011) Impact of Peg-interferon-alpha-2A therapy on the evolution of JAk2 and TET2 mutated clones in polycythemia vera. Haematologica, 96(Suppl. 2), A1062-A1445.
23. Knapper, S., Burnett, A.K., Littlewood, T., Kell, W.J., Agrawal, S., Chopra, R., Clark, R., Levis, M.J. & Small, D. (2006) A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy. Blood, 108, 3262-3270.
24. Komrokji, R.S., Wadleigh, M., Seymour, J.F., Roberts, A.W., To, L.B., Zhu, H.J. & Mesa, R.A. (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. Blood (ASH Annual Meeting Abstracts), 118, 282.
25. Kralovics, R., Passamonti, F., Buser, A.S., Teo, S.S., Tiedt, R., Passweg, J.R., Tichelli, A., Cazzola, M. & Skoda, R.C. (2005) A gain-of-function mutation of JAK2 in myeloproliferative disorders. New England Journal of Medicine, 352, 1779-1790.
26. Kroger, N., Alchalby, H., Klyuchnikov, E., Badbaran, A., Hildebrandt, Y., Ayuk, F., Bacher, U., Bock, O., Kvasnicka, M., Fehse, B. & Zander, A. (2009) JAK2-V617F-triggered preemptive and salvage adoptive immunotherapy with donor-lymphocyte infusion in patients with myelofibrosis after allogeneic stem cell transplantation. Blood, 113, 1866-1868.
27. Levine, R.L., Wadleigh, M., Cools, J., Ebert, B.L., Wernig, G., Huntly, B.J., Boggon, T.J., Wlodarska, I., Clark, J.J., Moore, S., Adelsperger, J., Koo, S., Lee, J.C., Gabriel, S., Mercher, T., D'Andrea, A., Frohling, S., Dohner, K., Marynen, P., Vandenberghe, P., Mesa, R.A., Tefferi, A., Griffin, J.D., Eck, M.J., Sellers, W.R., Meyerson, M., Golub, T.R., Lee, S.J. & Gilliland, D.G. (2005) Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell, 7, 387-397.
28. Liu, P.C., Caulder, E., Li, J., Waeltz, P., Margulis, A., Wynn, R., Becker-Pasha, M., Li, Y., Crowgey, E., Hollis, G., Haley, P., Sparks, R.B., Combs, A.P., Rodgers, J.D., Burn, T.C., Vaddi, K. & Fridman, J.S. (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. Clinical Cancer Research, 15, 6891-6900.
29. Ma, L., Zhao, B., Walgren, R., Clayton, J.A., Blosser, W.D., Burkholder, T.P. & Smith, M.C. (2010) Efficacy of LY2784544, a Small Molecule Inhibitor Selective for Mutant JAK2 Kinase, In JAK2 V617F-Induced Hematologic Malignancy Models. Blood (ASH Annual Meeting Abstracts), 116, 4087.
30. Mesa, R.A., Niblack, J., Wadleigh, M., Verstovsek, S., Camoriano, J., Barnes, S., Tan, A.D., Atherton, P.J., Sloan, J.A. & Tefferi, A. (2007) The burden of fatigue and quality of life in myeloproliferative disorders (MPDs): an international Internet-based survey of 1179 MPD patients. Cancer, 109, 68-76.
31. Mesa, R.A., Pardanani, A.D., Hussein, K., Wu, W., Schwager, S., Litzow, M.R., Hogan, W.J. & Tefferi, A. (2010) Phase1/-2 study of Pomalidomide in myelofibrosis. American Journal of Hematology, 85, 129-130.
32. Mesa, R., Kantarjian, H. & Shields, A. (2011) Results using the Modified Myelofibrosis Symptom Assessment Form (MFSAF v2.0) in COMFORT-I: a randomized, double-blind phase III trial of JAK1/2 inhibitor ruxolitinib vs. placebo in myelofibrosis (MF). Haematologica, 96(6, Suppl. 2), Abstract 0912.
33. Moliterno, A.R., Hexner, E., Roboz, G.J., Carroll, M., Luger, S., Mascarenhas, J., Hoffman, R. & Bensen-Kennedy, D.M. (2009) 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), 114, 753.
34. Oh, S.T., Simonds, E.F., Jones, C., Hale, M.B., Goltsev, Y., Gibbs, Jr, K.D., Merker, J.D., Zehnder, J.L., Nolan, G.P. & Gotlib, J. (2010) Novel mutations in the inhibitory adaptor protein LNK drive JAK-STAT signaling in patients with myeloproliferative neoplasms. Blood, 116, 988-992.
35. Paquette, R., Sokal, L., Shah, N.P., Silver, R.T., List, A.F., Clary, D.O., Bui, L.A. & Talpaz, M. (2008) A phase I study of XL019, a selective JAK2 inhibitor, in patients with polycythemia vera. Blood (ASH Annual Meeting Abstracts), 112, Abstract 2810.
36. Pardanani, A.D., Levine, R.L., Lasho, T., Pikman, Y., Mesa, R.A., Wadleigh, M., Steensma, D.P., Elliott, M.A., Wolanskyj, A.P., Hogan, W.J., McClure, R.F., Litzow, M.R., Gilliland, D.G. & Tefferi, A. (2006) MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood, 108, 3472-3476.
37. Pardanani, A., Gotlib, J., Jamieson, C., Cortes, J., Talpaz, M., Stone, R., Silverman, M.H., Shorr, J., Gilliland, D.G. & Tefferi, A. (2009a) A phase I study of TG101348, a selective JAK2 inhibitor, in myelofibrosis: clinical response is accompanied by significant reduction in JAK2V617F allele burden. Blood (ASH Annual Meeting Abstracts), 114, Abstract 755.
38. Pardanani, A., Lasho, T., Smith, G., Burns, C.J., Fantino, E. & Tefferi, A. (2009b) 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.
39. Pardanani, A., Gotlib, J.R., Jamieson, C., Cortes, J.E., Talpaz, M., Stone, R.M., Silverman, M.H., Gilliland, D.G., Shorr, J. & Tefferi, A. (2011a) Safety and Efficacy of TG101348, a Selective JAK2 Inhibitor, in Myelofibrosis. Journal of Clinical Oncology, 29, 789-796.
40. Pardanani, A., Gotlib, J., Jamieson, C., Cortes, J.E., Talpaz, M., Stone, R., Gao, G., Zhang, J., Neumann, F. & Tefferi, A. (2011b) SAR302503: interim Safety, Efficacy and Long-Term Impact on JAK2 V617F Allele Burden in a Phase I/II Study in Patients with Myelofibrosis. Blood (ASH Annual Meeting Abstracts), 118, 3838.
41. Pardanani, A., Gotlib, J., Gupta, V., Roberts, A.W., Wadleigh, M., Sirhan, S., Litzow, M.R., Hogan, W.J., Begna, K., Smith, G., Bavisotto, L.M., Kowalski, M. & Tefferi, A. (2011c) An Expanded Multicenter Phase I/II Study of CYT387, a JAK- 1/2 Inhibitor for the Treatment of Myelofibrosis. Blood (ASH Annual Meeting Abstracts), 118, 3849.
42. Parganas, E., Wang, D., Stravopodis, D., Topham, D.J., Marine, J.C., Teglund, S., Vanin, E.F., Bodner, S., Colamonici, O.R., van Deursen, J.M., Grosveld, G. & Ihle, J.N. (1998) Jak2 is essential for signaling through a variety of cytokine receptors. Cell, 93, 385-395.
43. Quintas-Cardama, A., Vaddi, K., Liu, P., Manshouri, T., Li, J., Scherle, P.A., Caulder, E., Wen, X., Li, Y., Waeltz, P., Rupar, M., Burn, T., Lo, Y., Kelley, J., Covington, M., Shepard, S., Rodgers, J.D., Haley, P., Kantarjian, H., Fridman, J.S. & Verstovsek, S. (2010) Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood, 115, 3109-3117.
44. Saharinen, P. & Silvennoinen, O. (2002) The pseudokinase domain is required for suppression of basal activity of Jak2 and Jak3 tyrosine kinases and for cytokine-inducible activation of signal transduction. Journal of Biological Chemistry, 277, 47954-47963.
45. Samuelson, S., Sandmaier, B.M., Heslop, H.E., Popat, U., Carrum, G., Champlin, R.E., Storb, R., Prchal, J.T., Gooley, T.A. & Deeg, H.J. (2011) Allogeneic haematopoietic cell transplantation for myelofibrosis in 30 patients 60-78 years of age. British Journal of Haematology, 153, 76-82.
46. Santos, F.P., Kantarjian, H.M., Jain, N., Manshouri, T., Thomas, D.A., Garcia-Manero, G., Kennedy, D., Estrov, Z., Cortes, J. & Verstovsek, S. (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.
47. Scherber, R., Dueck, A.C., Johansson, P., Barbui, T., Barosi, G., Vannucchi, A.M., Passamonti, F., Andreasson, B., Ferarri, M.L., Rambaldi, A., Samuelsson, J., Birgegard, G., Tefferi, A., Harrison, C.N., Radia, D. & Mesa, R.A. (2011) The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF): international Prospective Validation and Reliability Trial in 402 patients. Blood, 118, 401-408.
48. Scott, L.M., Tong, W., Levine, R.L., Scott, M.A., Beer, P.A., Stratton, M.R., Futreal, P.A., Erber, W.N., McMullin, M.F., Harrison, C.N., Warren, A.J., Gilliland, D.G., Lodish, H.F. & Green, A.R. (2007) JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. New England Journal of Medicine, 356, 459-468.
49. Shah, N., Olszynski, P., Sokal, L., Verstovsek, S., Hoffman, R., List, A.F., Cortes, J., Kantarjian, H.M., Gilliland, D.G., Clary, D.O., Bui, L.A. & Wadleigh, M. (2008) A phase I study of XL019, a selective JAK2 inhibitor, in patients with primary myelofibrosis, post-polycythemia vera, or post-essential thrombocythemia myelofibrosis. Blood, 112, Abstract 98.
50. Shide, K., Kameda, T., Markovtsov, V., Matsunaga, T., Shimoda, H., Hidaka, T., Katayose, K., Kubuki, Y., Bhamidipati, S., Park, G., Torneros, A., Duan, M., Hitoshi, Y. & Shimoda, K. (2009) Efficacy of R723, a Potent and Selective JAK2 Inhibitor, in JAK2 V617F-Induced Murine MPD Model. Blood (ASH Annual Meeting Abstracts), 11, Abstract 3897.
51. Tefferi, A., Barosi, G., Mesa, R.A., Cervantes, F., Deeg, H.J., Reilly, J.T., Verstovsek, S., Dupriez, B., Silver, R.T., Odenike, O., Cortes, J., Wadleigh, M., Solberg, Jr, L.A., Camoriano, J.K., Gisslinger, H., Noel, P., Thiele, J., Vardiman, J.W., Hoffman, R., Cross, N.C., Gilliland, D.G. & Kantarjian, H. (2006) 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, 108, 1497-1503.
52. Tefferi, A., Kantarjian, H.M. & Pardanani, A.D. (2008) The Clinical Phenotype of Myelofibrosis Encompasses a Chronic Inflammatory State That Is Favorably Altered by INCB018424, a Selective Inhibitor of JAK1/2. Blood (ASH Annual Meeting Abstracts), 112, Abstract 2804.
53. Tefferi, A., Litzow, M.R. & Pardanani, A. (2011) Long-term outcome of treatment with ruxolitinib in myelofibrosis. New England Journal of Medicine, 365, 1455-1457.
54. Tyner, J.W., Bumm, T.G., Deininger, J., Wood, L., Aichberger, K.J., Loriaux, M.M., Druker, B.J., Burns, C.J., Fantino, E. & Deininger, M.W. (2010) CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms. Blood, 115, 5232-5240.
55. Vainchenker, W., Delhommeau, F., Constantinescu, S.N. & Bernard, O.A. (2011) New mutations and pathogenesis of myeloproliferative neoplasms. Blood, 118, 1723-1735.
56. Vardiman, J.W., Thiele, J., Arber, D.A., Brunning, R.D., Borowitz, M.J., Porwit, A., Harris, N.L., Le Beau, M.M., Hellstrom-Lindberg, E., Tefferi, A. & Bloomfield, C.D. (2009) The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood, 114, 937-951.
57. Verstovsek, S., Odenike, O., Scott, B., Estrov, Z., Cortes, J., Thomas, D.A., Wood, J., Ethirajulu, K., Lowe, A., Zhu, H.J., Kantarjian, H. & Deeg, H.J. (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.
58. Verstovsek, S., Kantarjian, H., Mesa, R.A., Pardanani, A.D., Cortes-Franco, J., Thomas, D.A., Estrov, Z., Fridman, J.S., Bradley, E.C., Erickson-Viitanen, S., Vaddi, K., Levy, R. & Tefferi, A. (2010a) Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. New England Journal of Medicine, 363, 1117-1127.
59. Verstovsek, S., Passamonti, F., Rambaldi, A., Barosi, G., Rosen, P.J., Levy, R., Bradley, E., Garrett, W., Vaddi, K., Contel, N., Sandor, V., Huber, R.M., Schacter, L.P., Rumi, E., Gattoni, E., Antonioli, E., Pieri, L., Cazzola, M., Kantarjian, H., Barbui, T. & Vannucchi, A.M. (2010b) Durable Responses with the JAK1/JAK2 Inhibitor, INCB018424, In Patients with Polycythemia Vera (PV) and Essential Thrombocythemia (ET) Refractory or Intolerant to Hydroxyurea (HU). Blood (ASH Annual Meeting Abstracts), 116, 313.
60. Verstovsek, S., Mesa, R.A., Gotlib, J., Levy, R.S., Gupta, V., DiPersio, J.F., Catalano, J., Deininger, M.W., Miller, C.W., Silver, R.T., Talpaz, M., Winton, E.F., Harvey, Jr, J.H., Arcasoy, M.O., Hexner, E., Lyons, R.M., Paquette, R., Raza, A., Vaddi, K., Erickson-Viitanen, S., Sun, W., Sandor, V.A. & Kantarjian, H.M. (2011a) Consistent Benefit of Ruxolitinib Over Placebo in Spleen Volume Reduction and Symptom Improvement Across Subgroups and Overall Survival Advantage: results From COMFORT-I. Blood (ASH Annual Meeting Abstracts), 118, Abstract 278.
61. Verstovsek, S., Kantarjian, H.M., Estrov, Z., Cortes, J.E., Thomas, D.A., Kadia, T., Pierce, S., Cazzola, M., Rumi, E., Morra, E., Pungolino, E., Caramazza, D. & Passamonti, F. (2011b) Comparison of Outcomes of Advanced Myelofibrosis Patients Treated with Ruxolitinib (INCB018424) to Those of a Historical Control Group: survival Advantage of Ruxolitinib Therapy. Blood (ASH Annual Meeting Abstracts), 118, Abstract 793.
62. Verstovsek, S., Mesa, R.A., Gotlib, J., Levy, R.S., Gupta, V., DiPersio, J.F., Catalano, J.V., Deininger, M., Miller, C., Silver, R.T., Talpaz, M., Winton, E.F., Harvey, Jr, J.H., Arcasoy, M.O., Hexner, E., Lyons, R.M., Paquette, R., Raza, A., Vaddi, K., Erickson-Viitanen, S., Koumenis, I.L., Sun, W., Sandor, V. & Kantarjian, H.M. (2012) A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. The New England Journal of Medicine, 366, 799-807.
63. Wernig, G., Kharas, M.G., Okabe, R., Moore, S.A., Leeman, D.S., Cullen, D.E., Gozo, M., McDowell, E.P., Levine, R.L., Doukas, J., Mak, C.C., Noronha, G., Martin, M., Ko, Y.D., Lee, B.H., Soll, R.M., Tefferi, A., Hood, J.D. & Gilliland, D.G. (2008) Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera. Cancer Cell, 13, 311-320.
64. Wilks, A.F. (1989) Two putative protein-tyrosine kinases identified by application of the polymerase chain reaction. Proceedings of the National Academy of Sciences of the United States of America, 86, 1603-1607.
65. Wilks, A.F., Harpur, A.G., Kurban, R.R., Ralph, S.J., Zurcher, G. & Ziemiecki, A. (1991) Two novel protein-tyrosine kinases, each with a second phosphotransferase-related catalytic domain, define a new class of protein kinase. Molecular and Cellular Biology, 11, 2057-2065.