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Is JAK2V617F Mutation the Only Factor for Thrombosis in Philadelphia-Negative Chronic Myeloproliferative Neoplasms?

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Abstract

The most common genetic disorder in Philadelphia negative chronic myeloproliferative neoplasms is the JAK2-V617F mutation. In the present study, we aimed to determine risk factors for thrombosis in patients with essential thrombocytosis and polycythemia vera. We screened the medical records of 101 patients. Risk factors which may predict thrombosis were recorded. Venous thrombosis (VT) before diagnosis was significantly higher in JAK2 positive patients. VT after diagnosis was similar in JAK2 positive and negative groups, and was significantly higher in elderly patients. Treatment places importance on the JAK2 mutation under unmodifiable cardiovascular risk factors such as advanced age after diagnosis.

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References

  1. Dameshek W (1951) Some speculations on the myeloproliferative syndromes. Blood 6(4):372–375

    CAS  PubMed  Google Scholar 

  2. Vainchenker W, Delhommeau F, Constantinescu SN, Bernard OA (2011) New mutations and pathogenesis of myeloproliferative neoplasms. Blood 118(7):1723–1735. doi:10.1182/blood-2011-02-292102

    Article  CAS  PubMed  Google Scholar 

  3. Barbui T, Finazzi G, Falanga A (2013) Myeloproliferative neoplasms and thrombosis. Blood 122(13):2176–2184. doi:10.1182/blood-2013-03-460154

    Article  CAS  PubMed  Google Scholar 

  4. De Stefano V, Fiorini A, Rossi E, Za T, Farina G, Chiusolo P, Sica S, Leone G (2007) Incidence of the JAK2 V617F mutation among patients with splanchnic or cerebral venous thrombosis and without overt chronic myeloproliferative disorders. J Thromb Haemost 5(4):708–714. doi:10.1111/j.1538-7836.2007.02424.x

    Article  PubMed  Google Scholar 

  5. Kiladjian JJ (2012) The spectrum of JAK2-positive myeloproliferative neoplasms. Hematol Educ Prog Am Soc Hematol Am Soc Hematol Educ Prog 2012:561–566. doi:10.1182/asheducation-2012.1.561

    Google Scholar 

  6. Barosi G, Bergamaschi G, Marchetti M, Vannucchi AM, Guglielmelli P, Antonioli E, Massa M, Rosti V, Campanelli R, Villani L, Viarengo G, Gattoni E, Gerli G, Specchia G, Tinelli C, Rambaldi A, Barbui T, Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto Italian Registry of M (2007) JAK2 V617F mutational status predicts progression to large splenomegaly and leukemic transformation in primary myelofibrosis. Blood 110(12):4030–4036. doi:10.1182/blood-2007-07-099184

    Article  CAS  PubMed  Google Scholar 

  7. Heller PG, Lev PR, Salim JP, Kornblihtt LI, Goette NP, Chazarreta CD, Glembotsky AC, Vassallu PS, Marta RF, Molinas FC (2006) JAK2V617F mutation in platelets from essential thrombocythemia patients: correlation with clinical features and analysis of STAT5 phosphorylation status. Eur J Haematol 77(3):210–216. doi:10.1111/j.1600-0609.2006.00688.x

    Article  CAS  PubMed  Google Scholar 

  8. Cheung B, Radia D, Pantelidis P, Yadegarfar G, Harrison C (2006) The presence of the JAK2 V617F mutation is associated with a higher haemoglobin and increased risk of thrombosis in essential thrombocythaemia. Br J Haematol 132(2):244–245. doi:10.1111/j.1365-2141.2005.05858.x

    Article  CAS  PubMed  Google Scholar 

  9. Finazzi G, Rambaldi A, Guerini V, Carobbo A, Barbui T (2007) Risk of thrombosis in patients with essential thrombocythemia and polycythemia vera according to JAK2 V617F mutation status. Haematologica 92(1):135–136

    Article  PubMed  Google Scholar 

  10. Ziakas PD (2008) Effect of JAK2 V617F on thrombotic risk in patients with essential thrombocythemia: measuring the uncertain. Haematologica 93(9):1412–1414. doi:10.3324/haematol.12970

    Article  PubMed  Google Scholar 

  11. Dahabreh IJ, Zoi K, Giannouli S, Zoi C, Loukopoulos D, Voulgarelis M (2009) Is JAK2 V617F mutation more than a diagnostic index? A meta-analysis of clinical outcomes in essential thrombocythemia. Leuk Res 33(1):67–73. doi:10.1016/j.leukres.2008.06.006

    Article  CAS  PubMed  Google Scholar 

  12. Lussana F, Caberlon S, Pagani C, Kamphuisen PW, Buller HR, Cattaneo M (2009) Association of V617F Jak2 mutation with the risk of thrombosis among patients with essential thrombocythaemia or idiopathic myelofibrosis: a systematic review. Thromb Res 124(4):409–417. doi:10.1016/j.thromres.2009.02.004

    Article  CAS  PubMed  Google Scholar 

  13. Vannucchi AM, Antonioli E, Guglielmelli P, Longo G, Pancrazzi A, Ponziani V, Bogani C, Ferrini PR, Rambaldi A, Guerini V, Bosi A, Barbui T, Consortium MPDR (2007) Prospective identification of high-risk polycythemia vera patients based on JAK2(V617F) allele burden. Leukemia 21(9):1952–1959. doi:10.1038/sj.leu.2404854

    Article  CAS  PubMed  Google Scholar 

  14. Carobbio A, Finazzi G, Antonioli E, Guglielmelli P, Vannucchi AM, Dellacasa CM, Salmoiraghi S, Delaini F, Rambaldi A, Barbui T (2009) JAK2V617F allele burden and thrombosis: a direct comparison in essential thrombocythemia and polycythemia vera. Exp Hematol 37(9):1016–1021. doi:10.1016/j.exphem.2009.06.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Tefferi A, Lasho TL, Schwager SM, Strand JS, Elliott M, Mesa R, Li CY, Wadleigh M, Lee SJ, Gilliland DG (2006) The clinical phenotype of wild-type, heterozygous, and homozygous JAK2V617F in polycythemia vera. Cancer 106(3):631–635. doi:10.1002/cncr.21645

    Article  CAS  PubMed  Google Scholar 

  16. Bellanne-Chantelot C, Chaumarel I, Labopin M, Bellanger F, Barbu V, De Toma C, Delhommeau F, Casadevall N, Vainchenker W, Thomas G, Najman A (2006) Genetic and clinical implications of the Val617Phe JAK2 mutation in 72 families with myeloproliferative disorders. Blood 108(1):346–352. doi:10.1182/blood-2005-12-4852

    Article  CAS  PubMed  Google Scholar 

  17. Falanga A, Marchetti M (2012) Thrombotic disease in the myeloproliferative neoplasms. Hematol Educ Prog Am Soc Hematol Am Soc Hematol Educ Prog 2012:571–581. doi:10.1182/asheducation-2012.1.571

    Google Scholar 

  18. Vardiman JW, Harris NL, Brunning RD (2002) The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 100(7):2292–2302. doi:10.1182/blood-2002-04-1199

    Article  CAS  PubMed  Google Scholar 

  19. Passamonti F, Rumi E, Pietra D, Elena C, Boveri E, Arcaini L, Roncoroni E, Astori C, Merli M, Boggi S, Pascutto C, Lazzarino M, Cazzola M (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(9):1574–1579. doi:10.1038/leu.2010.148

    Article  CAS  PubMed  Google Scholar 

  20. Alvarez-Larran A, Cervantes F, Pereira A, Arellano-Rodrigo E, Perez-Andreu V, Hernandez-Boluda JC, Ayats R, Salvador C, Muntanola A, Bellosillo B, Vicente V, Hernandez-Nieto L, Burgaleta C, Xicoy B, Besses C (2010) Observation versus antiplatelet therapy as primary prophylaxis for thrombosis in low-risk essential thrombocythemia. Blood 116(8):1205–1210. doi:10.1182/blood-2010-01-263319 quiz 1387

    Article  CAS  PubMed  Google Scholar 

  21. Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, Barbui T, European Collaboration on Low-Dose Aspirin in Polycythemia Vera I (2004) Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med 350(2):114–124. doi:10.1056/NEJMoa035572

    Article  CAS  PubMed  Google Scholar 

  22. Cortelazzo S, Finazzi G, Ruggeri M, Vestri O, Galli M, Rodeghiero F, Barbui T (1995) Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med 332(17):1132–1136. doi:10.1056/NEJM199504273321704

    Article  CAS  PubMed  Google Scholar 

  23. Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D, Wilkins BS, van der Walt JD, Reilly JT, Grigg AP, Revell P, Woodcock BE, Green AR, United Kingdom Medical Research Council Primary Thrombocythemia S (2005) Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med 353(1):33–45. doi:10.1056/NEJMoa043800

    Article  CAS  PubMed  Google Scholar 

  24. Gisslinger H, Gotic M, Holowiecki J, Penka M, Thiele J, Kvasnicka HM, Kralovics R, Petrides PE, Group AS (2013) Anagrelide compared with hydroxyurea in WHO-classified essential thrombocythemia: the ANAHYDRET Study, a randomized controlled trial. Blood 121(10):1720–1728. doi:10.1182/blood-2012-07-443770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Barbui T, Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodeghiero F, Randi ML, Bertozzi I, Gisslinger H, Buxhofer-Ausch V, De Stefano V, Betti S, Rambaldi A, Vannucchi AM, Tefferi A (2012) Development and validation of an International Prognostic Score of thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis). Blood 120(26):5128–5133. doi:10.1182/blood-2012-07-444067 quiz 5252

    Article  CAS  PubMed  Google Scholar 

  26. Bates SM (2012) D-dimer assays in diagnosis and management of thrombotic and bleeding disorders. Semin Thromb Hemost 38(7):673–682. doi:10.1055/s-0032-1326782

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by authors themselves.

Authors Contributions

MS.U., M.B. and G.E.P. designed the study; M.B., M.M. and E.G.U. provided the patients’ samples; M.S.U. and M.A. performed statistical analysis, M.A. designed the tables; A.M.D. and E.A. performed the experiments and analyzed the data; E.A. and G.E.P. reviewed the manuscript. All authors contributed to the writing of the manuscript.

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Authors and Affiliations

  1. Department of Hematology, Trakya University Medical Faculty, Edirne, Turkey

    Mehmet Sevki Uyanik, Gulsum Emel Pamuk, Muhammet Maden, Elif Gulsum Umit & Muzaffer Demir

  2. Department of Internal Medicine, Trakya University Medical Faculty, Edirne, Turkey

    Mehmet Baysal, Mustafa Akker & Erkan Aydogdu

  3. Eski Yildiz Cad. Park Apt. No:22, Daire:18, 34349, Besiktas-Istanbul, Turkey

    Gulsum Emel Pamuk

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  1. Mehmet Sevki Uyanik
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  2. Mehmet Baysal
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Correspondence to Gulsum Emel Pamuk.

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The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.

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Uyanik, M.S., Baysal, M., Pamuk, G.E. et al. Is JAK2V617F Mutation the Only Factor for Thrombosis in Philadelphia-Negative Chronic Myeloproliferative Neoplasms?. Indian J Hematol Blood Transfus 32, 262–267 (2016). https://doi.org/10.1007/s12288-015-0578-2

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  • DOI: https://doi.org/10.1007/s12288-015-0578-2

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