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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 21, 2005 Accepted July 9, 2006 Mutation of JAK2 in the myeloproliferative disorders: timing, clonality studies, cytogenetic associations and role in leukemic transformation Peter J Campbell, E J Baxter, Philip A Beer, Linda M Scott, Anthony J Bench, Brian J Huntly, Wendy N Erber, Rajko Kusec, Thomas S Larsen, Stephane Giraudier, Marie-Caroline Le Bousse-Kerdiles, Martin Griesshammer, John T Reilly, Betty Y Cheung, Claire N Harrison, and Anthony R Green* Haematology, University of Cambridge, Cambridge, UK Haematology, Addenbrooke's Hospital, Cambridge, UK Haematology & Clinical Chemistry, Merkur University Hospital, Zagreb, Croatia Haematology & Pathology, Odense University Hospital, Denmark INSERM U362, Villejuif & Laboratoire d'Hematologie, Henri Mondor Hospital, France INSERM U602, Institut Andre Lwoff, Universite Paris 11, Villejuif, France Department of Internal Medicine III, University of Ulm, Ulm, Germany Haematology, Royal Hallamshire Hospital, Sheffield, UK Haematology, St Thomas's Hospital, London, UK * Corresponding author; email: arg1000{at}cam.ac.uk. 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-negative essential thrombocythemia do not commonly progress to become V617F-positive. 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 20q deletion or trisomy 9 being V617F-positive. 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-positive granulocytes. Our results demonstrate that inherent XCIP variability between granulocytes and T cells produces a systematically biased pattern of results which may be misinterpreted as evidence for an excess of clonally- derived granulocytes, an observation which limits the utility of XCIP analysis in this context. Lastly we studied four patients with V617F-positive myeloproliferative disorders who subsequently developed acute myeloid leukemia. In three patients the leukemic cells were V617F-negative, suggesting that in these patients the leukemia arose in a V617F-negative 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. 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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. 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