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Blood, 1 August 2007, Vol. 110, No. 3, pp. 1013-1021. Prepublished online as a Blood First Edition Paper on March 27, 2007; DOI 10.1182/blood-2006-10-054940. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-10-054940v1 110/3/1013    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 Dupont, S. Articles by Delhommeau, F. Search for Related Content PubMed PubMed Citation Articles by Dupont, S. Articles by Delhommeau, F. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 30, 2006 Accepted March 20, 2007 The JAK2 V617F mutation triggers erythropoietin hypersensitivity and terminal erythroid amplification in primary cells from patients with polycythemia vera Sabrina Dupont, Aline Masse, Chloe James, Irene Teyssandier, Yann Lecluse, Frederic Larbret, Valerie Ugo, Patrick Saulnier, Serge Koscielny, Jean Pierre Le Couedic, Nicole Casadevall, William Vainchenker, and Francois Delhommeau* U790, Inserm, Universite Paris Sud, Institut Gustave Roussy, Villejuif, France Inserm E217, Universite Victor Segalen Bordeaux 2, Bordeaux, France Laboratoire d'Hematologie, AP-HP, Hopital Hotel-Dieu et Hopital Saint-Antoine, Paris, France Service Commun de Cytometrie, Institut Gustave Roussy, Villejuif, France Laboratoire d'Hematologie, Centre Hospitalier Universitaire de Brest, Brest, France Laboratoire de Recherche Translationnelle, Institut Gustave Roussy, Villejuif, France Department of Biostatisticsand Epidemiology, Institut Gustave Roussy, Villejuif, France Universite Pierre et Marie Curie, Paris, France * Corresponding author; email: fdelhommeau{at}igr.fr. The JAK2 V617F mutation is frequent in polycythemia vera (PV) and essential thrombocythemia (ET). Using quantitative PCR, we find that high amounts of JAK2 V617F in PV correlate with increased granulocytes and high levels of hemoglobin and endogenous erythroid colony formation. We detect normal progenitors and those that are heterozygous or homozygous for the mutation by genotyping ET and PV clonal immature and committed progenitors. In PV patients, we distinguish homozygous profiles with normal, heterozygous and homozygous progenitors from heterozygous profiles with only heterozygous and normal progenitors. PV patients with a heterozygous profile have more mutated committed progenitors than other PV and ET patients, suggesting a selective amplification of mutated cells in the early phases of hematopoiesis. We demonstrate that mutated erythroid progenitors are more sensitive to erythropoietin than normal progenitors, and that most homozygous erythroid progenitors are erythropoietin independent. Moreover, we observe a greater in vitro erythroid amplification and a selective advantage in vivo for mutated cells in late stages of hematopoiesis. These results suggest that for PV, erythrocytosis can occur through two mechanisms: terminal erythroid amplification triggered by JAK2 V617F homozygosity, and a two-step process including the upstream amplification of heterozygous cells that may involve additional molecular events. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: The amount of JAK2 617V>F matters Josef T. Prchal Blood 2007 110: 796-797. [Full Text] [PDF] This article has been cited by other articles: L. Pieri, C. Bogani, P. Guglielmelli, M. Zingariello, R. A. Rana, N. Bartalucci, A. Bosi, and A. M. 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Med., May 28, 2009; 360(22): 2289 - 2301. [Abstract] [Full Text] [PDF] S. Schnittger, U. Bacher, C. Haferlach, T. Geer, P. Muller, J. Mittermuller, P. Petrides, R. Schlag, R. Sandner, J. Selbach, et al. Detection of JAK2 exon 12 mutations in 15 patients with JAK2V617F negative polycythemia vera Haematologica, March 1, 2009; 94(3): 414 - 418. [Abstract] [Full Text] [PDF] C. James, F. Mazurier, S. Dupont, R. Chaligne, I. Lamrissi-Garcia, M. Tulliez, E. Lippert, F.-X. Mahon, J.-M. Pasquet, G. Etienne, et al. The hematopoietic stem cell compartment of JAK2V617F-positive myeloproliferative disorders is a reflection of disease heterogeneity Blood, September 15, 2008; 112(6): 2429 - 2438. [Abstract] [Full Text] [PDF] I. Plo, M. Nakatake, L. Malivert, J.-P. de Villartay, S. Giraudier, J.-L. Villeval, L. Wiesmuller, and W. 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