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Blood, 1 October 2009, Vol. 114, No. 14, pp. 3018-3023. Prepublished online as a Blood First Edition Paper on June 18, 2009; DOI 10.1182/blood-2009-03-209916. This Article Full Text (PDF) Supplemental Methods and Table All Versions of this Article: blood-2009-03-209916v1 114/14/3018    most recent e-Letter: Submit a Response Alert me when this article is cited Alert me when e-Letters are posted 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 Lambert, J. R Articles by Gale, R. E Search for Related Content PubMed PubMed Citation Articles by Lambert, J. R Articles by Gale, R. E Related Collections Related Article in Blood Online Social Bookmarking                         What's this?  Previous Article  |  Next Article  Submitted March 10, 2009 Accepted June 7, 2009 In essential thrombocythemia, multiple JAK2-V617F clones are present in most mutant-positive patients: a new disease paradigm Jonathan R Lambert, Tamara Everington, David C Linch, and Rosemary E Gale* Department of Haematology, UCL Cancer Institute, London, United Kingdom * Corresponding author; email: rosemary.gale{at}ucl.ac.uk. In essential thrombocythemia (ET), the JAK2-V617F mutation is usually restricted to a subpopulation of neutrophils and platelets, and production of JAK2 wild-type (WT) platelets is not suppressed. Non-mutated precursor cells may, therefore, be susceptible to the acquisition of further JAK2 mutations. We used a common single nucleotide polymorphism (SNP) in the JAK2 coding sequence to genotype V617F alleles obtained either by allele-specific restriction enzyme digestion (RED) or by cloning. Both SNP alleles were detected in JAK2 mutant-positive alleles from neutrophils of 10 of 11 ET patients studied using RED compared to zero out of five with polycythemia vera. These results were confirmed in cloned products from five ET patients and indicate the occurrence of at least two separate JAK2 mutation events in the majority of ET patients investigated. In a further ET patient, JAK2 mutant-positive erythroid colonies with either X-allele inactivated were detected, demonstrating they could not have arisen from a common clonal precursor. These results indicate that at least two independent JAK2-V617F events occur commonly in ET patients, and they may arise on a polyclonal background. The presence of a JAK2 mutation in ET patients should not, therefore, be equated with a malignant disease. CiteULike    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this? Related Article in Blood Online: Same mutation, different allele Karl J. Aichberger, Angela G. Fleischman, and Michael W. Deininger Blood 2009 114: 2853-2854. [Full Text] [PDF] This article has been cited by other articles: P. A. Beer, C. A. Ortmann, P. J. Campbell, and A. R. Green Independently acquired biallelic JAK2 mutations are present in a minority of patients with essential thrombocythemia Blood, August 12, 2010; 116(6): 1013 - 1014. [Full Text] [PDF] B. L. Stein and A. R. Moliterno Primary Myelofibrosis and the Myeloproliferative Neoplasms: The Role of Individual Variation JAMA, June 23, 2010; 303(24): 2513 - 2518. [Abstract] [Full Text] [PDF] A. V. Jones, P. J. Campbell, P. A. Beer, S. Schnittger, A. M. Vannucchi, K. Zoi, M. J. Percy, M. F. McMullin, L. M. Scott, W. Tapper, et al. The JAK2 46/1 haplotype predisposes to MPL-mutated myeloproliferative neoplasms Blood, June 3, 2010; 115(22): 4517 - 4523. [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]

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