The future of JAK inhibition in myelofibrosis and beyond

Blood Reviews

Volumn 28, Issue 5, 2014, Pages 189-196

  Mascarenhas, John O ^a   Cross, Nicholas C P ^b   Mesa, Ruben A ^c  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^c MAYO CLINIC   (United States)

Author keywords

JAK; Myelofibrosis; Myeloproliferative neoplasms; Polycythemia vera; Ruxolitinib

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; 5 CHLORO N2 [1 (5 FLUORO 2 PYRIMIDINYL)ETHYL] N4 (5 METHYL 1H PYRAZOL 3 YL) 2,4 PYRIMIDINEDIAMINE; AZACITIDINE; BMS 911543; DANAZOL; FEDRATINIB; GANDOTINIB; HYDROXYUREA; JANUS KINASE; JANUS KINASE 2; JANUS KINASE 2 INHIBITOR; JANUS KINASE INHIBITOR; LENALIDOMIDE; LESTAURTINIB; LY 278544; MOMELOTINIB; NS 018; PACRITINIB; PANOBINOSTAT; PEGINTERFERON ALPHA2A; PLACEBO; RECOMBINANT ERYTHROPOIETIN; RUXOLITINIB; SONIDEGIB; STAT PROTEIN; TRIACYLGLYCEROL LIPASE; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; PROTEIN KINASE INHIBITOR;

ALOPECIA AREATA; ANEMIA; BLOOD TOXICITY; BONE MARROW SUPPRESSION; BREAST CANCER; CHRONIC MYELOID LEUKEMIA; CYTOPENIA; DIARRHEA; DIZZINESS; DRUG DOSE ESCALATION; DRUG WITHDRAWAL; GASTROINTESTINAL TOXICITY; HEADACHE; HODGKIN DISEASE; HUMAN; JAK2 GENE; LARGE CELL LYMPHOMA; LIVER FUNCTION TEST; MYELODYSPLASTIC SYNDROME; MYELOFIBROSIS; MYELOID METAPLASIA; MYELOPROLIFERATIVE NEOPLASM; NAUSEA; NEUROPATHY; NEUROTOXICITY; NEUTROPHIL COUNT; NONHUMAN; OVERALL SURVIVAL; PANCREAS CANCER; PATHOGENESIS; POINT MUTATION; POLYCYTHEMIA VERA; PRIORITY JOURNAL; REMISSION; REVIEW; RHEUMATOID ARTHRITIS; SOLID TUMOR; SOMATIC MUTATION; SPLENOMEGALY; SURVIVAL RATE; T CELL LEUKEMIA; THROMBOCYTE COUNT; THROMBOCYTOPENIA; THROMBOTIC THROMBOCYTOPENIC PURPURA; WERNICKE ENCEPHALOPATHY; ANTAGONISTS AND INHIBITORS; METABOLISM; PRIMARY MYELOFIBROSIS; SIGNAL TRANSDUCTION;

ANTINEOPLASTIC AGENTS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; HUMANS; JANUS KINASES; PRIMARY MYELOFIBROSIS; PROTEIN KINASE INHIBITORS; SIGNAL TRANSDUCTION;

EID: 84906935504     PISSN: 0268960X     EISSN: 15321681     Source Type: Journal    
DOI: 10.1016/j.blre.2014.06.002     Document Type: Review

References (87)

1. Parganas E., Wang D., Stravopodis D., Topham D.J., Marine J.C., Teglund S., et al. Jak2 is essential for signaling through a variety of cytokine receptors. Cell 1998, 93:385-395.
2. Quintas-Cardama A., Verstovsek S. Molecular pathways: Jak/STAT pathway: mutations, inhibitors, and resistance. Clin Cancer Res 2013, 19:1933-1940.
3. Levine R.L., Pardanani A., Tefferi A., Gilliland D.G. Role of JAK2 in the pathogenesis and therapy of myeloproliferative disorders. Nat Rev Cancer 2007, 7:673-683.
4. Silva M., Richard C., Benito A., Sanz C., Olalla I., Fernandez-Luna J.L. Expression of Bcl-x in erythroid precursors from patients with polycythemia vera. N Engl J Med 1998, 338:564-571.
5. Sansone P., Bromberg J. Targeting the interleukin-6/Jak/stat pathway in human malignancies. J Clin Oncol 2012, 30:1005-1014.
6. 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, 60:549-552.
7. Rosenwald A., Wright G., Leroy K., Yu X., Gaulard P., Gascoyne R.D., et al. Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diffuse large B cell lymphoma related to Hodgkin lymphoma. J Exp Med 2003, 198:851-862.
8. Lenz G., Wright G.W., Emre N.C., Kohlhammer H., Dave S.S., Davis R.E., et al. Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways. Proc Natl Acad Sci U S A 2008, 105:13520-13525.
9. Traer E., MacKenzie R., Snead J., Agarwal A., Eiring A.M., O'Hare T., et al. Blockade of JAK2-mediated extrinsic survival signals restores sensitivity of CML cells to ABL inhibitors. Leukemia 2012, 26:1140-1143.
10. Jelinek J., Oki Y., Gharibyan V., Bueso-Ramos C., Prchal J.T., Verstovsek S., et al. JAK2 mutation 1849G>T is rare in acute leukemias but can be found in CMML, Philadelphia chromosome-negative CML, and megakaryocytic leukemia. Blood 2005, 106:3370-3373.
11. Lee J.W., Kim Y.G., Soung Y.H., Han K.J., Kim S.Y., Rhim H.S., et al. The JAK2 V617F mutation in de novo acute myelogenous leukemias. Oncogene 2006, 25:1434-1436.
12. Walters D.K., Mercher T., Gu T.L., O'Hare T T., Tyner J.W., Loriaux M., et al. Activating alleles of JAK3 in acute megakaryoblastic leukemia. Cancer Cell 2006, 10:65-75.
13. Xiang Z., Zhao Y., Mitaksov V., Fremont D.H., Kasai Y., Molitoris A., et al. Identification of somatic JAK1 mutations in patients with acute myeloid leukemia. Blood 2008, 111:4809-4812.
14. Mullighan C.G., Zhang J., Harvey R.C., Collins-Underwood J.R., Schulman B.A., Phillips L.A., et al. JAK mutations in high-risk childhood acute lymphoblastic leukemia. Proc Natl Acad Sci U S A 2009, 106:9414-9418.
15. Baxter E.J., Scott L.M., Campbell P.J., East C., Fourouclas N., Swanton S., et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005, 365:1054-1061.
16. James C., Ugo V., Le Couedic J.P., Staerk J., Delhommeau F., Lacout C., et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 2005, 434:1144-1148.
17. Kralovics R., Passamonti F., Buser A.S., Teo S.S., Tiedt R., Passweg J.R., et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005, 352:1779-1790.
18. Levine R.L., Wadleigh M., Cools J., Ebert B.L., Wernig G., Huntly B.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.
19. Zhao R., Xing S., Li Z., Fu X., Li Q., Krantz S.B., et al. Identification of an acquired JAK2 mutation in polycythemia vera. J Biol Chem 2005, 280:22788-22792.
20. Spivak J.L. The chronic myeloproliferative disorders: clonality and clinical heterogeneity. Semin Hematol 2004, 41:1-5.
21. Cervantes F., Dupriez B., Pereira A., Passamonti F., Reilly J.T., Morra E., 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.
22. Cross N.C. Genetic and epigenetic complexity in myeloproliferative neoplasms. Hematol Am Soc Hematol Educ Program 2011, 2011:208-214.
23. Hookham M.B., Elliott J., Suessmuth Y., Staerk J., Ward A.C., Vainchenker W., et al. The myeloproliferative disorder-associated JAK2 V617F mutant escapes negative regulation by suppressor of cytokine signaling 3. Blood 2007, 109:4924-4929.
24. 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, 19:283-294.
25. Martinez-Aviles L., Besses C., Alvarez-Larran A., Cervantes F., Hernandez-Boluda J.C., Bellosillo B. JAK2 exon 12 mutations in polycythemia vera or idiopathic erythrocytosis. Haematologica 2007, 92:1717-1718.
26. Pardanani A., Lasho T.L., Finke C., Hanson C.A., Tefferi A. Prevalence and clinicopathologic correlates of JAK2 exon 12 mutations in JAK2V617F-negative polycythemia vera. Leukemia 2007, 21:1960-1963.
27. Scott L.M., Tong W., Levine R.L., Scott M.A., Beer P.A., Stratton M.R., et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med 2007, 356:459-468.
28. Ma W., Zhang X., Wang X., Zhang Z., Yeh C.H., Uyeji J., et al. MPL mutation profile in JAK2 mutation-negative patients with myeloproliferative disorders. Diagn Mol Pathol 2011, 20:34-39.
29. Dos Santos L.C., Ribeiro J.C., Silva N.P., Cerutti J., da Silva M.R., Chauffaille Mde L. Cytogenetics, JAK2 and MPL mutations in polycythemia vera, primary myelofibrosis and essential thrombocythemia. Rev Bras Hematol Hemoter 2011, 33:417-424.
30. Baran-Marszak F., Magdoud H., Desterke C., Alvarado A., Roger C., Harel S., et al. Expression level and differential JAK2-V617F-binding of the adaptor protein Lnk regulates JAK2-mediated signals in myeloproliferative neoplasms. Blood 2010, 116:5961-5971.
31. Pardanani A., Lasho T., Finke C., Oh S.T., Gotlib J., Tefferi A. LNK mutation studies in blast-phase myeloproliferative neoplasms, and in chronic-phase disease with TET2, IDH, JAK2 or MPL mutations. Leukemia 2010, 24:1713-1718.
32. Oh S.T., Simonds E.F., Jones C., Hale M.B., Goltsev Y., Gibbs K.D., et al. Novel mutations in the inhibitory adaptor protein LNK drive JAK-STAT signaling in patients with myeloproliferative neoplasms. Blood 2010, 116:988-992.
33. Martinez-Aviles L., Besses C., Alvarez-Larran A., Torres E., Serrano S., Bellosillo B. TET2, ASXL1, IDH1, IDH2, and c-CBL genes in JAK2- and MPL-negative myeloproliferative neoplasms. Ann Hematol 2012, 91:533-541.
34. Grand F.H., Hidalgo-Curtis C.E., Ernst T., Zoi K., Zoi C., McGuire C., et al. Frequent CBL mutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms. Blood 2009, 113:6182-6192.
35. Klampfl T., Gisslinger H., Harutyunyan A.S., Nivarthi H., Rumi E., Milosevic J.D., et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med 2013, 369:2379-2390.
36. Nangalia J., Massie C.E., Baxter E.J., Nice F.L., Gundem G., Wedge D.C., et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med 2013, 369:2391-2405.
37. Rampal R., Al-Shahrour F., Abdel-Wahab O., Patel J., Brunel J.P., Mermel C.H., et al. Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis. Blood 2014, 123:e123-e133.
38. Milosevic J.D., Kralovics R. Genetic and epigenetic alterations of myeloproliferative disorders. Int J Hematol 2013, 97:183-197.
39. Voso M.T., Fabiani E., Fianchi L., Falconi G., Criscuolo M., Santangelo R., et al. Mutations of epigenetic regulators and of the spliceosome machinery in therapy-related myeloid neoplasms and in acute leukemias evolved from chronic myeloproliferative diseases. Leukemia 2013, 27:982-985.
40. Zhang S.J., Abdel-Wahab O. Disordered epigenetic regulation in the pathophysiology of myeloproliferative neoplasms. Curr Hematol Malig Rep 2012, 7:34-42.
41. Guglielmelli P., Lasho T.L., Rotunno G., Score J., Mannarelli C., Pancrazzi A., et al. The number of prognostically detrimental mutations and prognosis in primary myelofibrosis: an international study of 797 patients. Leukemia 2014, 10.1038/leu.2014.76.
42. Beer P.A., Delhommeau F., LeCouedic J.P., Dawson M.A., Chen E., Bareford D., et al. Two routes to leukemic transformation after a JAK2 mutation-positive myeloproliferative neoplasm. Blood 2010, 115:2891-2900.
43. Delhommeau F., Dupont S., Della Valle V., James C., Trannoy S., Masse A., et al. Mutation in TET2 in myeloid cancers. N Engl J Med 2009, 360:2289-2301.
44. Chen E., Beer P.A., Godfrey A.L., Ortmann C.A., Li J., Costa-Pereira A.P., et al. Distinct clinical phenotypes associated with JAK2V617F reflect differential STAT1 signaling. Cancer Cell 2010, 18:524-535.
45. Tefferi A., Lasho T.L., Finke C., Belachew A.A., Wassie E.A., Ketterling R.P., et al. Type 1 vs type 2 calreticulin mutations in primary myelofibrosis: differences in phenotype and prognostic impact. Leukemia 2014, [Epub ahead of print]. 10.1038/leu.2014.83.
46. Tefferi A., Wassie E.A., Guglielmelli P., Gangat N., Belachew A.A., Lasho T.L., et al. Type 1 versus Type 2 calreticulin mutations in essential thrombocythemia: a collaborative study of 1027 patients. Am J Hematol 2014, 10.1002/ajh.23743.
47. Passamonti F., Cervantes F., Vannucchi A.M., Morra E., Rumi E., Pereira A., et al. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). Blood 2010, 115:1703-1708.
48. Mascarenhas J., Hoffman R. Myeloproliferative neoplasms: new translational therapies. Mt Sinai J Med 2010, 77:667-683.
49. Keohane C., Radia D.H., Harrison C.N. Treatment and management of myelofibrosis in the era of JAK inhibitors. Biologics 2013, 7:189-198.
50. Sonbol M.B., Firwana B., Zarzour A., Morad M., Rana V., Tiu R.V. Comprehensive review of JAK inhibitors in myeloproliferative neoplasms. Ther Adv Hematol 2013, 4:15-35.
51. Quintas-Cardama A., Vaddi K., Liu P., Manshouri T., Li J., Scherle P.A., et al. Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood 2010, 115:3109-3117.
52. Verstovsek S., Kantarjian H., Mesa R.A., Pardanani A.D., Cortes-Franco J., Thomas D.A., et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med 2010, 363:1117-1127.
53. Harrison C., Kiladjian J.J., Al-Ali H.K., Gisslinger H., Waltzman R., Stalbovskaya V., et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 2012, 366:787-798.
54. Verstovsek S., Mesa R.A., Gotlib J., Levy R.S., Gupta V., DiPersio J.F., et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 2012, 366:799-807.
55. Zhou T., Georgeon S., Moser R., Moore D.J., Caflisch A., Hantschel O. Specificity and mechanism-of-action of the JAK2 tyrosine kinase inhibitors ruxolitinib and SAR302503 (TG101348). Leukemia 2014, 28:404-407.
56. Pardanani A., Gotlib J.R., Jamieson C., Cortes J.E., Talpaz M., Stone R.M., et al. Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis. J Clin Oncol 2011, 29:789-796.
57. Pardanani A., Harrison C.N., Cortes J.E., Cervantes F., Mesa R.A., Milligan D., et al. Results of a randomized, double-blind, placebo-controlled phase III study (JAKARTA) of the JAK2-selective inhibitor fedratinib (SAR302503) in patients with myelofibrosis (MF). Blood 2013, 122. 21, [abstr 393].
58. Harrison C.N., Schaap N., Zweegman S., Jourdan E., Kiladjian J.J., Cervantes F., et al. Efficacy and safety of fedratinib (SAR302503/TG101348) in patients with intermediate- or high-risk myelofibrosis (MF), post-polycythemia vera (PV) MF, or post-essential thrombocythemia (ET) MF previously treated with ruxolitinib: interim results from a phase II study (JAKARTA-2). Blood 2013, 122. 21, [abstr 661].
59. Pardanani A., Laborde R.R., Lasho T.L., Finke C., Begna K., Al-Kali A., et al. Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis. Leukemia 2013, 27:1322-1327.
60. Pardanani A., Gotlib J., Gupta V., Roberts A.W., Wadleigh M., Sirhan S., et al. Update on the long-term efficacy and safety of momelotinib, a JAK1 and JAK2 inhibitor, for the treatment of myelofibrosis. Blood 2013, 122. 21, [abstr 108].
61. Komrokji R.S., Wadleigh M., Seymour J.F., Roberts A.W., Wadleigh M., Sirhan S., et al. 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 2011, 118. 21, [abstr 282].
62. Verstovsek S., Dean J.P., Cernohous P., Komrokji R.S., Seymour J.F., Mesa R.A., et al. Pacritinib, a dual JAK2/FLT3 inhibitor: an integrated efficacy and safety analysis of phase II trial data in patients with primary and secondary myelofibrosis (MF) and platelet counts ≤100,000/μl. Am Soc Hematol Annu Meet 2013, 122:395.
63. Santos F.P., Kantarjian H.M., Jain N., Manshouri T., Thomas D.A., Garcia-Manero G., 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.
64. Hexner E., Roboz G., Hoffman R., Luger S., Mascarenhas J., Carroll M., et al. Open-label study of oral CEP-701 (lestaurtinib) in patients with polycythaemia vera or essential thrombocythaemia with JAK2-V617F mutation. Br J Haematol 2013, 164:83-93.
65. Pardanani A., Roberts A.W., Seymour J.F., Burbury K., Verstovsek S., Kantarjian H.M., et al. BMS-911543, a selective JAK2 inhibitor: a multicenter phase 1/2a study in myelofibrosis. Am Soc Hematol Annu Meet 2013, 122:664.
66. Verstovsek S., Mesa R., Salama M.E., Giles J.L.k., Pitou C., Zimmermann A.H., et al. Phase I study of LY2784544, a JAK2 selective inhibitor, in patients with myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET). Am Soc Hematol Annu Meet 2013, 122:665.
67. Kantarjian H.M., Silver R.T., Komrokji R.S., Mesa R.A., Tacke R., Harrison C.N. Ruxolitinib for myelofibrosis-an update of its clinical effects. Clin Lymphoma Myeloma Leuk 2013, 13:638-645.
68. Verstovsek S. Therapeutic advances in myeloproliferative neoplasms: the role of new-small molecule inhibitors. Am Soc Clin Oncol Educ book/ ASCO Am Soc Clin Oncol Meet 2012, 32:406-410.
69. Cervantes F., Kiladjian J., Niederwieser D., Sirulnik A., Stalbovskaya V., McQuity M., et al. Long-term safety, efficacy, and survival findings from Comfort-II, a phase 3 study comparing ruxolitinib with best available therapy (BAT) for the treatment of myelofibrosis (MF). Blood 2012, 120. [abstr 801].
70. Cervantes F., Mesa R., Harrison C. JAK inhibitors: beyond spleen and symptoms?. Haematologica 2013, 98:160-162.
71. Gale R.P., Barosi G., Barbui T., Cervantes F., Dohner K., Dupriez B., et al. What are RBC-transfusion-dependence and -independence?. Leuk Res 2011, 35:8-11.
72. Verstovsek S., Mesa R., Gotlib J., Levy R.S., Gupta V., Dipersio J.F., et al. Long-term outcomes of ruxolitinib therapy in patients with myelofibrosis: 3-year update from COMFORT-I. Am Soc Hematol 2013, 122:396.
73. Mascarenhas J., Hoffman R. A comprehensive review and analysis of the effect of ruxolitinib therapy on the survival of patients with myelofibrosis. Blood 2013, 121:4832-4837.
74. Tefferi A. Pathogenesis of myelofibrosis with myeloid metaplasia. J Clin Oncol 2005, 23:8520-8530.
75. Martyre M.C., Magdelenat H., Bryckaert M.C., Laine-Bidron C., Calvo F. Increased intraplatelet levels of platelet-derived growth factor and transforming growth factor-beta in patients with myelofibrosis with myeloid metaplasia. Br J Haematol 1991, 77:80-86.
76. Thiele J., Kvasnicka H.M., Mullauer L., Buxhofer-Ausch V., Gisslinger B., Gisslinger H. Essential thrombocythemia versus early primary myelofibrosis: a multicenter study to validate the WHO classification. Blood 2011, 117:5710-5718.
77. Kvasnicka H., Thiele J., Bueso-Ramos C.E., Sun W., Cortes J., Kantarjian H.M., et al. Long-term intervention effects on bone marrow morphology in myelofibrosis: patients treated with ruxolitinib and best available therapy. Haematologica 2013, 98. s1, [abstr S591].
78. McLornan D., Harrison C. Combination therapies in myeloproliferative neoplasms: why do we need them and how to identify potential winners?. J Cell Mol Med 2013, 17:1410-1414.
79. Mascarenhas J. Rationale for combination therapy in myelofibrosis. Best Pract Res Clin Haematol 2014, [in press].
80. Kroger N., Alchalby H., Ditschkowski M., Wolf D., Wulf G., Zabelina T., et al. Ruxolitinib as pretreatment before allogeneic stem cell transplantation for myelofibrosis. Blood 2013, 122. 21, [abstr 392].
81. Robin M., Francois S., Huynh A., Cassinat B., Bay J.O., Cornillon J., et al. Ruxolitinib before allogeneic hematopoietic stem cell transplantation (HSCT) In patients with myelofibrosis: a preliminary descriptive report of the JAK ALLO study, a phase II trial sponsored by Goelams-FIM in collaboration with the Sfgmtc. Blood 2013, 122. 21, [abstr 306].
82. Barbui T., Barosi G., Birgegard G., Cervantes F., Finazzi G., Griesshammer M., et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol 2011, 29:761-770.
83. Barosi G., Tefferi A., Barbui T. Do current response criteria in classical Ph-negative myeloproliferative neoplasms capture benefit for patients?. Leukemia 2012, 26:1148-1149.
84. Barbui T. How to manage thrombosis in myeloproliferative neoplasms. Curr Opin Oncol 2011, 23:654-658.
85. Scherber R., Dueck A.C., Johansson P., Barbui T., Barosi G., Vannucchi A.M., et al. The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF): international prospective validation and reliability trial in 402 patients. Blood 2011, 118:401-408.
86. Verstovsek S., Passamonti F., Rambaldi A., Barosi G., Rosen P.J., Rumi E., et al. A phase 2 study of ruxolitinib, an oral JAK1 and JAK2 inhibitor, in patients with advanced polycythemia vera who are refractory or intolerant to hydroxyurea. Cancer 2014, 120:513-520.
87. Tibes R., Mesa R.A. Emerging drugs for polycythemia vera. Expert Opin Emerg Drugs 2013, 18:393-404.