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Blood, 1 December 2007, Vol. 110, No. 12, pp. 4030-4036. Prepublished online as a Blood First Edition Paper on August 21, 2007; DOI 10.1182/blood-2007-07-099184. This Article Full Text (PDF) Supplemental Appendix All Versions of this Article: blood-2007-07-099184v1 110/12/4030    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 Barosi, G. Articles by Barbui, T. Search for Related Content PubMed PubMed Citation Articles by Barosi, G. Articles by Barbui, T. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 2, 2007 Accepted August 16, 2007 JAK2 V617F mutational status predicts progression to large splenomegaly and leukemic transformation in primary myelofibrosis Giovanni Barosi*, Gaetano Bergamaschi, Monia Marchetti, Alessandro M Vannucchi, Paola Guglielmelli, Elisabetta Antonioli, Margherita Massa, Vittorio Rosti, Rita Campanelli, Laura Villani, Gianluca Viarengo, Elisabetta Gattoni, Giancarla Gerli, Giorgina Specchia, Carmine Tinelli, Alessandro Rambaldi, and Tiziano Barbui Unit of Clinical Epidemiology, and Center for the Study of Myelofibrosis, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy Unit of Clinical Medicine I, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy Department of Hematology, University of Florence, Florence, Italy Laboratory of Biotechnology, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy Transplant Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy Unit of Clinical Immunology, Immunohematology, and Transfusion Service, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy Division of Hematology, Ospedale San Paolo, Milan, Italy Hematology Department, University of Bari, Bari, Italy Epidemiology and Biometric Unit, IRCCS Policlinico S. Matteo Foundation, Pavia, Italy Division of Hematology, Ospedali Riuniti di Bergamo, Bergamo, Italy * Corresponding author; email: barosig{at}smatteo.pv.it. Few investigators have evaluated the usefulness of the JAK2 V617F mutation for explaining the phenotypic variations and for predicting the risk of major clinical events in primary myelofibrosis (PMF). In a transversal survey we assayed by allele specific PCR the JAK2 V617F mutational status in 304 PMF patients. Multiple DNA samples were collected prospectively from 64 patients, and a highly sensitive quantitative PCR was used as a confirmatory test. In a longitudinal prospective study we determined the progression rate to clinically relevant outcomes in 174 patients who had JAK2 mutation determined at diagnosis. JAK2 V617F was identified in 63.4% of patients. None of the V617F-negative patients who were sequentially genotyped progressed to become V617F-positive, while progression rate from heterozygous to homozygous mutation was 10 per 100 patient-years. JAK2 V617F mutation contributed to hemoglobin, aquagenic pruritus and platelet count variability, while homozygous mutation was independently associated with higher white-blood cell count, larger spleen size, and greater need for cytoreductive therapies. Adjusting for conventional risk factors, V617F mutation independently predicted the evolution towards large splenomegaly, need of splenectomy, and leukemic transformation. We conclude that JAK2 V617F genotype deems to be considered in any future risk stratification of PMF patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: MPL and JAK2 exon 12 mutations in patients with the Budd-Chiari syndrome or extrahepatic portal vein obstruction Gaetano M. Bergamaschi, Massimo Primignani, Giovanni Barosi, Federica M. Fabris, Laura Villani, Raffaella Reati, Alessandra Dell'Era, and Pier M. Mannucci Blood 2008 111: 4418. [Full Text] [PDF] Clinical profile of homozygous JAK2 617V>F 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, for the Italian Group for Malignant Hematologic Disorders of the Adult–Myeloproliferative Disorder Working Party (GIMEMA-MPD WP) Blood 2007 110: 840-846. [Abstract] [Full Text] [PDF] This article has been cited by other articles: G. Piaggio, V. Rosti, M. Corselli, F. Bertolotti, G. Bergamaschi, S. Pozzi, D. Imperiale, B. Chiavarina, E. Bonetti, F. Novara, et al. Endothelial colony-forming cells from patients with chronic myeloproliferative disorders lack the disease-specific molecular clonality marker Blood, October 1, 2009; 114(14): 3127 - 3130. [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] F. Girodon, G. Bonicelli, C. Schaeffer, M. Mounier, S. Carillo, I. Lafon, P. M. Carli, I. Janoray, E. Ferrant, and M. Maynadie Significant increase in the apparent incidence of essential thrombocythemia related to new WHO diagnostic criteria: a population-based study Haematologica, June 1, 2009; 94(6): 865 - 869. [Abstract] [Full Text] [PDF] A. M. Vannucchi, P. Guglielmelli, and A. 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[Abstract] [Full Text] [PDF] A. Pancrazzi, P. Guglielmelli, V. Ponziani, G. Bergamaschi, A. Bosi, G. Barosi, and A. M. Vannucchi A Sensitive Detection Method for MPLW515L or MPLW515K Mutation in Chronic Myeloproliferative Disorders with Locked Nucleic Acid-Modified Probes and Real-Time Polymerase Chain Reaction J. Mol. Diagn., September 1, 2008; 10(5): 435 - 441. [Abstract] [Full Text] [PDF] A. M. Vannucchi, E. Antonioli, P. Guglielmelli, A. Pancrazzi, V. Guerini, G. Barosi, M. Ruggeri, G. Specchia, F. Lo-Coco, F. Delaini, et al. 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] 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] G. M. Bergamaschi, M. Primignani, G. Barosi, F. M. Fabris, L. Villani, R. Reati, A. Dell'Era, and P. M. Mannucci MPL and JAK2 exon 12 mutations in patients with the Budd-Chiari syndrome or extrahepatic portal vein obstruction Blood, April 15, 2008; 111(8): 4418 - 4418. [Full Text] [PDF] F. Passamonti, E. Rumi, M. Caramella, C. Elena, L. Arcaini, E. Boveri, C. Del Curto, D. Pietra, L. Vanelli, P. Bernasconi, et al. A dynamic prognostic model to predict survival in post-polycythemia vera myelofibrosis Blood, April 1, 2008; 111(7): 3383 - 3387. [Abstract] [Full Text] [PDF] A. Rambaldi, T. Barbui, and G. Barosi From Palliation to Epigenetic Therapy in Myelofibrosis Hematology, January 1, 2008; 2008(1): 83 - 91. [Abstract] [Full Text] [PDF] A. Tefferi Management of Myeloproliferative Neoplasms and the Promise of Targeted Therapy ASCO Educational Book, January 1, 2008; 2008(1): 346 - 348. [Abstract] [Full Text] [PDF]

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