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Blood, 15 September 2008, Vol. 112, No. 6, pp. 2429-2438. Prepublished online as a Blood First Edition Paper on July 8, 2008; DOI 10.1182/blood-2008-02-137877. This Article Full Text (PDF) All Versions of this Article: blood-2008-02-137877v1 112/6/2429    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 James, C. Articles by de Verneuil, H. Search for Related Content PubMed PubMed Citation Articles by James, C. Articles by de Verneuil, H. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 6, 2008 Accepted July 2, 2008 The hematopoietic stem cell compartment of JAK2V617F positive myeloproliferative disorders is a reflection of disease heterogeneity Chloe James*, Frederic Mazurier, Sabrina Dupont, Ronan Chaligne, Isabelle Lamrissi-Garcia, Micheline Tulliez, Eric Lippert, Francois-Xavier Mahon, Jean-Max Pasquet, Gabriel Etienne, Francois Delhommeau, Stephane Giraudier, William Vainchenker, and Hubert de Verneuil INSERM U876, Universite Bordeaux, Bordeaux, France Universite V. Segalen Bordeaux 2, Bordeaux, France INSERM UMR790, Institut Gustave Roussy, Villejuif, France Universite Paris XI, Villejuif, France Laboratoire d'anatomie et de cytologie pathologiques, Hopital Cochin, AP-HP, Paris, France Laboratoire d'hematologie, CHU de Bordeaux, Bordeaux, France Departement d'hematologie, Institut Bergonie, Bordeaux, France Labatoire d'hematologie, Hopital Saint Antoine, AP-HP, Paris, France Labatoire d'hematologie, Hopital Henri Mondor, AP-HP, Creteil, France * Corresponding author; email: chloe.james{at}wanadoo.fr. The JAK2V617F somatic point mutation has been described in patients with myeloproliferative disorders (MPD). Despite this progress, it remains unknown how a single JAK2 mutation causes three different MPD phenotypes, polycythemia vera (PV), essential thrombocythemia and primitive myelofibrosis (PMF). Using an in vivo xenotransplantation assay in nonobese diabetic-severe combined immunodeficient (NOD/SCID) mice, we tested whether disease heterogeneity was associated with quantitative or qualitative differences in the hematopoietic stem cell (HSC) compartment. We show that the HSC compartment of PV and PMF patients contains JAK2V617F-positive long-term, multipotent and self-renewing cells. However, the proportion of JAK2V617F and JAK2 wild type SCID repopulating cells (SRC) was dramatically different in these diseases, without major modifications of the self-renewal and proliferation capacities for JAK2V617F SRC. These experiments provide new insights into the pathogenesis of JAK2V617F MPD and demonstrate that a JAK2 inhibitor needs to target the HSC compartment for optimal disease control in classical MPD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I. Plo, Y. Zhang, J.-P. Le Couedic, M. Nakatake, J.-M. Boulet, M. Itaya, S. O. Smith, N. Debili, S. N. Constantinescu, W. Vainchenker, et al. An activating mutation in the CSF3R gene induces a hereditary chronic neutrophilia J. Exp. Med., August 3, 2009; 206(8): 1701 - 1707. [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] 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]

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