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Blood, 1 August 2007, Vol. 110, No. 3, pp. 840-846. Prepublished online as a Blood First Edition Paper on March 22, 2007; DOI 10.1182/blood-2006-12-064287. This Article Full Text (PDF) Supplemental Appendix and Tables All Versions of this Article: blood-2006-12-064287v1 110/3/840    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Vannucchi, A. M. Articles by Barbui, T. Search for Related Content PubMed PubMed Citation Articles by Vannucchi, A. M. Articles by Barbui, T. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 29, 2006 Accepted March 19, 2007 Clinical profile of homozygous JAK2V617F mutation in patients with polycythemia vera or essential thrombocythemia Alessandro M. Vannucchi*, Elisabetta Antonioli, Paola Guglielmelli, Alessandro Rambaldi, Giovanni Barosi, Roberto Marchioli, Rosa Maria Marfisi, Guido Finazzi, Vittoria Guerini, Fabrizio Fabris, Maria Luigia Randi, Valerio De Stefano, Sabrina Caberlon, Agostino Tafuri, Marco Ruggeri, Giorgina Specchia, Vincenzo Liso, Edoardo Rossi, Enrico Pogliani, Luigi Gugliotta, Alberto Bosi, and Tiziano Barbui Dipartimento di Ematologia, Universita de Firenze, Firenze, Italy Divisione di Ematologia, Ospedali Riuniti, Bergamo, Italy Unita di Epidemiologia Clinica, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy Laboratorio di Epidemiologia, Clinica della malattie Cardiovascolari, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy Dipartimento di Scienze Medico-Chirugiche, Sezione Medicina Interna, Universita di Padova, Padova, Italy Dipartimento di Ematologia, Universita Cattolica del Sacro Cuore, Roma, Italy Unita di Ematologia, Ospedale San Paolo, Universita di Milano, Milano, Italy Divisione di Ematologia, Dipartimento di Biotecnologie Cellulari e Ematologia, Universita, Roma, Italy Dipartimento di Ematologia, Centro per l'Emofilia e la Trombosi, Ospedale San Bortolo, Vicenza, Italy Dipartimento di Ematologia, Universita di Bari, Bari, Italy Servizio di Immunoematologia e Medicina Trasfusionale, Ospedale L. Sacco, Milano, Italy Unita di Ematologia, Ospedale S. Gerardo, Monza, Italy Divisione di Ematologia, Ospedale Riuniti, Reggio Emilia, Italy * Corresponding author; email: amvannucchi{at}unifi.it. JAK2V617F mutation occurs in an homozygous status in 25-30% of patients with polycythemia vera (PV) and 2-4% with essential thrombocythemia (ET). Whether homozygosity associates with distinct clinical phenotypes is still under debate. This retrospective multicentric study considered 118 JAK2V617F homozygous patients (104 PV, 14 ET) whose clinical characteristics were compared to those of 587 heterozygous and 257 wild-type patients. Irrespectively of their clinical diagnosis, homozygous were older, displayed higher leukocyte count and hematocrit value at diagnosis, and presented larger spleen volume. Aquagenic pruritus was significantly more common among homozygous PV patients. JAK2V617F homozygosity associated to more frequent evolution into secondary myelofibrosis in both PV and ET. After adjustement for gender, age, leukocytes and previous thrombosis in a multivariate analysis, homozygous ET patients displayed a significantly higher risk of cardiovascular events (HR 3.97, CI 95% 1.34-11.7; p=0.013) than wild-type (HR=1.0) or heterozygous (HR=1.49). No significant association of JAK2V617F homozygosity with thrombosis risk was observed in PV. Finally, JAK2V617F homozygous patients were more likely to receive chemotherapy for control of disease. We conclude that JAK2V617F homozygosity identifies PV or ET patients with a more symptomatic myeloproliferative disorder and is associated with a higher risk of major cardiovascular events in patients with ET. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: JAK2 V617F mutational status predicts progression to large splenomegaly and leukemic transformation in primary myelofibrosis Giovanni Barosi, Gaetano Bergamaschi, Monia Marchetti, Alessandro M. 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Vannucchi The JAK2V617 mutation induces constitutive activation and agonist hypersensitivity in basophils from patients with polycythemia vera Haematologica, November 1, 2009; 94(11): 1537 - 1545. [Abstract] [Full Text] [PDF] P. Guglielmelli, G. Barosi, G. Specchia, A. Rambaldi, F. Lo Coco, E. Antonioli, L. Pieri, A. Pancrazzi, V. Ponziani, F. Delaini, et al. Identification of patients with poorer survival in primary myelofibrosis based on the burden of JAK2V617F mutated allele Blood, August 20, 2009; 114(8): 1477 - 1483. [Abstract] [Full Text] [PDF] M. E. Salama, S. I. Swierczek, K. Hickman, A. Wilson, and J. T. Prchal Plasma quantitation of JAK2 mutation is not suitable as a clinical test: an artifact of storage Blood, July 2, 2009; 114(1): 223 - 224. [Full Text] [PDF] V. De Stefano, T. Za, E. Rossi, A. Fiorini, A. Ciminello, C. Luzzi, P. Chiusolo, S. Sica, and G. 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Characteristics and clinical correlates of MPL 515W>L/K mutation in essential thrombocythemia Blood, August 1, 2008; 112(3): 844 - 847. [Abstract] [Full Text] [PDF] J. L. Spivak and R. T. Silver The revised World Health Organization diagnostic criteria for polycythemia vera, essential thrombocytosis, and primary myelofibrosis: an alternative proposal Blood, July 15, 2008; 112(2): 231 - 239. [Full Text] [PDF] P. A. Beer, P. J. Campbell, L. M. Scott, A. J. Bench, W. N. Erber, D. Bareford, B. S. Wilkins, J. T. Reilly, H. C. Hasselbalch, R. Bowman, et al. MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort Blood, July 1, 2008; 112(1): 141 - 149. [Abstract] [Full Text] [PDF] A. Carobbio, E. Antonioli, P. Guglielmelli, A. M. Vannucchi, F. Delaini, V. Guerini, G. Finazzi, A. Rambaldi, and T. Barbui Leukocytosis and Risk Stratification Assessment in Essential Thrombocythemia J. Clin. Oncol., June 1, 2008; 26(16): 2732 - 2736. [Abstract] [Full Text] [PDF] J.-J. Kiladjian, F. Cervantes, F. W. G. Leebeek, C. Marzac, B. Cassinat, S. Chevret, D. Cazals-Hatem, A. Plessier, J.-C. Garcia-Pagan, S. D. Murad, et al. The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis: a report on 241 cases Blood, May 15, 2008; 111(10): 4922 - 4929. [Abstract] [Full Text] [PDF] S. Xing, T. H. Wanting, W. Zhao, J. Ma, S. Wang, X. Xu, Q. Li, X. Fu, M. Xu, and Z. J. Zhao Transgenic expression of JAK2V617F causes myeloproliferative disorders in mice Blood, May 15, 2008; 111(10): 5109 - 5117. [Abstract] [Full Text] [PDF] R. Tiedt, H. Hao-Shen, M. A. Sobas, R. Looser, S. Dirnhofer, J. Schwaller, and R. C. Skoda Ratio of mutant JAK2-V617F to wild-type Jak2 determines the MPD phenotypes in transgenic mice Blood, April 15, 2008; 111(8): 3931 - 3940. [Abstract] [Full Text] [PDF] P. M. Mannucci and F. Peyvandi Thrombophilia Screening: Little Role for the JAK2V617F Mutation Mayo Clin. Proc., April 1, 2008; 83(4): 398 - 399. [Full Text] [PDF] R. A. Mesa Steel to heal? MPD surgical conundrums Blood, January 15, 2008; 111(2): 474 - 474. [Full Text] [PDF] M. Ruggeri, F. Rodeghiero, A. Tosetto, G. Castaman, F. Scognamiglio, G. Finazzi, F. Delaini, C. Mico, A. M. Vannucchi, E. Antonioli, et al. Postsurgery outcomes in patients with polycythemia vera and essential thrombocythemia: a retrospective survey Blood, January 15, 2008; 111(2): 666 - 671. [Abstract] [Full Text] [PDF] E. Antonioli, P. Guglielmelli, G. Poli, C. Bogani, A. Pancrazzi, G. Longo, V. Ponziani, L. Tozzi, L. Pieri, V. Santini, et al. Influence of JAK2V617F allele burden on phenotype in essential thrombocythemia Haematologica, January 1, 2008; 93(1): 41 - 48. [Abstract] [Full Text] [PDF] G. Barosi, G. Bergamaschi, M. Marchetti, A. M. Vannucchi, P. Guglielmelli, E. Antonioli, M. Massa, V. Rosti, R. Campanelli, L. Villani, et al. JAK2 V617F mutational status predicts progression to large splenomegaly and leukemic transformation in primary myelofibrosis Blood, December 1, 2007; 110(12): 4030 - 4036. [Abstract] [Full Text] [PDF] R. A. Mesa Navigating the Evolving Paradigms in the Diagnosis and Treatment of Myeloproliferative Disorders Hematology, January 1, 2007; 2007(1): 355 - 362. [Abstract] [Full Text] [PDF] A. M. Vannucchi and T. Barbui Thrombocytosis and Thrombosis Hematology, January 1, 2007; 2007(1): 363 - 370. [Abstract] [Full Text] [PDF]

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