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Blood, 15 November 2006, Vol. 108, No. 10, pp. 3548-3555. Prepublished online as a Blood First Edition Paper on July 27, 2006; DOI 10.1182/blood-2005-12-013748. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2005-12-013748v1 108/10/3548    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Campbell, P. J. Articles by Green, A. R. Search for Related Content PubMed PubMed Citation Articles by Campbell, P. J. Articles by Green, A. R. Related Collections Neoplasia Oncogenes and Tumor Suppressors Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Mutation of JAK2 in the myeloproliferative disorders: timing, clonality studies, cytogenetic associations, and role in leukemic transformation Peter J. Campbell, E. Joanna Baxter, Philip A. Beer, Linda M. Scott, Anthony J. Bench, Brian J. P. Huntly, Wendy N. Erber, Rajko Kusec, Thomas Stauffer Larsen, Stéphane Giraudier, Marie-Caroline Le Bousse-Kerdilès, Martin Griesshammer, John T. Reilly, Betty Y. Cheung, Claire N. Harrison, and Anthony R. Green From the Department of Haematology, University of Cambridge, Cambridge, United Kingdom; Department of Haematology, Addenbrooke's Hospital, Cambridge, United Kingdom; Haematology and Clinical Chemistry Departments, Merkur University Hospital, Zagreb, Croatia; Haematology and Pathology Departments, Odense University Hospital, Denmark; Institut National de la Santé et de la Recherche Médicale (INSERM) U362, Villejuif and Laboratoire d'Hématologie, Henri Mondor Hospital, France; INSERM U602, Institut André Lwoff, Université Paris 11, Villejuif, France; Department of Internal Medicine III, University of Ulm, Ulm, Germany; Department of Haematology, Royal Hallamshire Hospital, Sheffield, United Kingdom; and Department of Haematology, St Thomas's Hospital, London, United Kingdom. The identification of an acquired mutation of JAK2 in patients with myeloproliferative disorders has raised questions about the relationship between mutation-positive and mutation-negative subtypes, timing of the JAK2 mutation, and molecular mechanisms of disease progression. Here we demonstrate that patients with V617F- essential thrombocythemia do not commonly progress to become V617F+. Consistent with the concept of distinct pathogenetic mechanisms, we show that patients with and without the JAK2 mutation have different patterns of cytogenetic abnormality, with virtually all patients carrying the 20q deletion or trisomy 9 being V617F+. We also investigated the existence of a "pre-JAK2" phase by comparing the proportion of clonally derived granulocytes, estimated from X-chromosome inactivation patterns (XCIPs), with the proportion of V617F+ granulocytes. Our results demonstrate that inherent XCIP variability between granulocytes and T cells produces a systematically biased pattern of results that may be misinterpreted as evidence for an excess of clonally derived granulocytes, an observation that limits the utility of XCIP analysis in this context. Lastly, we studied 4 patients with V617F+ myeloproliferative disorders who subsequently developed acute myeloid leukemia. In 3 patients the leukemic cells were V617F-, suggesting that in these patients the leukemia arose in a V617F- cell. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Cankovic, L. Whiteley, R. C. Hawley, R. J. Zarbo, and D. Chitale Clinical Performance of JAK2 V617F Mutation Detection Assays in a Molecular Diagnostics Laboratory: Evaluation of Screening and Quantitation Methods Am J Clin Pathol, November 1, 2009; 132(5): 713 - 721. [Abstract] [Full Text] [PDF] K. J. Aichberger, A. G. Fleischman, and M. W. Deininger Same mutation, different allele Blood, October 1, 2009; 114(14): 2853 - 2854. [Full Text] [PDF] J. R. Lambert, T. Everington, D. C. Linch, and R. E. Gale In essential thrombocythemia, multiple JAK2-V617F clones are present in most mutant-positive patients: a new disease paradigm Blood, October 1, 2009; 114(14): 3018 - 3023. [Abstract] [Full Text] [PDF] H. Haeno, R. L. Levine, D. G. Gilliland, and F. Michor A progenitor cell origin of myeloid malignancies PNAS, September 29, 2009; 106(39): 16616 - 16621. [Abstract] [Full Text] [PDF] F. H. Grand, C. E. Hidalgo-Curtis, T. Ernst, K. Zoi, C. Zoi, C. McGuire, S. Kreil, A. Jones, J. Score, G. Metzgeroth, et al. Frequent CBL mutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms Blood, June 11, 2009; 113(24): 6182 - 6192. [Abstract] [Full Text] [PDF] F. Delhommeau, S. Dupont, V. D. Valle, C. James, S. Trannoy, A. Masse, O. Kosmider, J.-P. Le Couedic, F. Robert, A. Alberdi, et al. Mutation in TET2 in Myeloid Cancers N. Engl. J. Med., May 28, 2009; 360(22): 2289 - 2301. [Abstract] [Full Text] [PDF] R. L. Levine and M. Carroll A Common Genetic Mechanism in Malignant Bone Marrow Diseases N. Engl. J. Med., May 28, 2009; 360(22): 2355 - 2357. [Full Text] [PDF] A. M. Vannucchi, P. Guglielmelli, and A. Tefferi Advances in Understanding and Management of Myeloproliferative Neoplasms CA Cancer J Clin, May 1, 2009; 59(3): 171 - 191. [Abstract] [Full Text] [PDF] F. X. Schaub, R. Jager, R. Looser, H. Hao-Shen, S. Hermouet, F. Girodon, A. Tichelli, H. Gisslinger, R. Kralovics, and R. C. Skoda Clonal analysis of deletions on chromosome 20q and JAK2-V617F in MPD suggests that del20q acts independently and is not one of the predisposing mutations for JAK2-V617F Blood, February 26, 2009; 113(9): 2022 - 2027. [Abstract] [Full Text] [PDF] A. Theocharides, J. R. Passweg, M. Medinger, R. Looser, S. Li, H. Hao-Shen, A. S. Buser, A. Gratwohl, A. Tichelli, and R. C. Skoda The allele burden of JAK2 mutations remains stable over several years in patients with myeloproliferative disorders Haematologica, December 1, 2008; 93(12): 1890 - 1893. [Abstract] [Full Text] [PDF] F. Passamonti, E. Rumi, L. Arcaini, E. Boveri, C. Elena, D. Pietra, S. Boggi, C. Astori, P. Bernasconi, M. Varettoni, et al. Prognostic factors for thrombosis, myelofibrosis, and leukemia in essential thrombocythemia: a study of 605 patients Haematologica, November 1, 2008; 93(11): 1645 - 1651. [Abstract] [Full Text] [PDF] R. L. Levine and D. G. Gilliland Myeloproliferative disorders Blood, September 15, 2008; 112(6): 2190 - 2198. [Abstract] [Full Text] [PDF] C. S. Tam, R. M. Nussenzveig, U. Popat, C. E. Bueso-Ramos, D. A. Thomas, J. A. Cortes, R. E. Champlin, S. E. Ciurea, T. Manshouri, S. M. Pierce, et al. The natural history and treatment outcome of blast phase BCR-ABL- myeloproliferative neoplasms Blood, September 1, 2008; 112(5): 1628 - 1637. [Abstract] [Full Text] [PDF] A. M. Vannucchi and P. Guglielmelli Molecular pathophysiology of Philadelphia-negative myeloproliferative disorders: beyond JAK2 and MPL mutations Haematologica, July 1, 2008; 93(7): 972 - 976. [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] C. James The JAK2V617F Mutation in Polycythemia Vera and Other Myeloproliferative Disorders: One Mutation for Three Diseases? Hematology, January 1, 2008; 2008(1): 69 - 75. [Abstract] [Full Text] [PDF] R. L. Levine and M. Heaney New Advances in the Pathogenesis and Therapy of Essential Thrombocythemia Hematology, January 1, 2008; 2008(1): 76 - 82. [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] P. J. Campbell and A. R. Green Methuselah conundrum: MPDs in the elderly Blood, September 1, 2007; 110(5): 1409 - 1409. [Full Text] [PDF] G. L. Chen and J. T. Prchal X-linked clonality testing: interpretation and limitations Blood, September 1, 2007; 110(5): 1411 - 1419. [Abstract] [Full Text] [PDF] M. A. Vickers JAK2 617V>F positive polycythemia rubra vera maintained by approximately 18 stochastic stem-cell divisions per year, explaining age of onset by a single rate-limiting mutation Blood, September 1, 2007; 110(5): 1675 - 1680. [Abstract] [Full Text] [PDF] A. M. Vannucchi, E. Antonioli, P. Guglielmelli, A. Rambaldi, G. Barosi, R. Marchioli, R. M. Marfisi, G. Finazzi, V. Guerini, F. Fabris, et al. Clinical profile of homozygous JAK2 617V>F mutation in patients with polycythemia vera or essential thrombocythemia Blood, August 1, 2007; 110(3): 840 - 846. [Abstract] [Full Text] [PDF] A. Theocharides, M. Boissinot, F. Girodon, R. Garand, S.-S. Teo, E. Lippert, P. Talmant, A. Tichelli, S. Hermouet, and R. C. Skoda Leukemic blasts in transformed JAK2-V617F-positive myeloproliferative disorders are frequently negative for the JAK2-V617F mutation. Blood, July 1, 2007; 110(1): 375 - 379. [Abstract] [Full Text] [PDF] R. Skoda The Genetic Basis of Myeloproliferative Disorders Hematology, January 1, 2007; 2007(1): 1 - 10. [Abstract] [Full Text] [PDF]

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