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Blood, 1 January 2007, Vol. 109, No. 1, pp. 71-77. Prepublished online as a Blood First Edition Paper on September 5, 2006; DOI 10.1182/blood-2006-03-007146. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-03-007146v1 109/1/71    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 Delhommeau, F. Articles by Giraudier, S. Search for Related Content PubMed PubMed Citation Articles by Delhommeau, F. Articles by Giraudier, S. Related Collections Hematopoiesis and Stem Cells Neoplasia Oncogenes and Tumor Suppressors Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Evidence that the JAK2 G1849T (V617F) mutation occurs in a lymphomyeloid progenitor in polycythemia vera and idiopathic myelofibrosis François Delhommeau1,3, Sabrina Dupont1, Carole Tonetti4, Aline Massé1, Isabelle Godin1, Jean-Pierre Le Couedic1, Najet Debili1, Patrick Saulnier5, Nicole Casadevall1,2, William Vainchenker1, and Stéphane Giraudier1,4, 1 Institut National de la Santé et de la Recherche Médicale (INSERM) unité (U) 790, Université Paris Sud, Institut Gustave Roussy, Villejuif, France; 2 Laboratoire d'Hématologie, Hôpital Hôtel-Dieu, Assistance Publique-Hôpitaux de Paris, France; 3 Laboratoire d'Hématologie, Hôpital Saint Antoine, Assistance Publique–Hôpitaux de Paris, Université Pierre et Marie Curie, Paris, France; 4 Laboratoire d'Hématologie, Hôpital Henri Mondor, Assistance Publique–Hôpitaux de Paris, Créteil, France; and 5 Laboratoire de Recherche Translationnelle, Institut Gustave Roussy, Villejuif, France The JAK2 V617F mutation has recently been described as an essential oncogenic event associated with polycythemia vera (PV), idiopathic myelofibrosis (IMF), and essential thrombocythemia. This mutation has been detected in all myeloid lineages but has not yet been detected in lymphoid cells. This raises the question whether this molecular event occurs in a true lymphomyeloid progenitor cell. In this work, we studied the presence of the mutation in peripheral blood cells and sorted B, T, and natural killer (NK) cells from PV and IMF. We detected the JAK2 V617F mutation in B and NK cells in approximately half the patients with IMF and a minority of those with PV. Moreover, in a few cases patients with IMF had mutated peripheral T cells. The mutation (homozygous or heterozygous) could be subsequently detected in B/NK/myeloid progenitors from PV and IMF, with a much higher frequency in clones derived from IMF. Using the fetal thymus organ culture (FTOC) assay, the mutation was also detected in all T-cell fractions derived from IMF and PV CD34+ cells. These results demonstrate that myeloproliferative disorders take their origin in a true myeloid/lymphoid progenitor cell but that their phenotype is related to a downstream selective proliferative advantage of the myeloid lineages. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Li, R. Kralovics, G. De Libero, A. Theocharides, H. Gisslinger, and R. C. Skoda Clonal heterogeneity in polycythemia vera patients with JAK2 exon12 and JAK2-V617F mutations Blood, April 1, 2008; 111(7): 3863 - 3866. [Abstract] [Full Text] [PDF] E. Rumi, F. Passamonti, M. G. Della Porta, C. Elena, L. Arcaini, L. Vanelli, C. Del Curto, D. Pietra, E. Boveri, C. Pascutto, et al. Familial Chronic Myeloproliferative Disorders: Clinical Phenotype and Evidence of Disease Anticipation J. Clin. Oncol., December 10, 2007; 25(35): 5630 - 5635. [Abstract] [Full Text] [PDF] R. Chaligne, C. James, C. Tonetti, R. Besancenot, J. P. Le Couedic, F. Fava, F. Mazurier, I. Godin, K. Maloum, F. Larbret, et al. Evidence for MPL W515L/K mutations in hematopoietic stem cells in primitive myelofibrosis Blood, November 15, 2007; 110(10): 3735 - 3743. [Abstract] [Full Text] [PDF] L. Nilsson, P. Eden, E. Olsson, R. Mansson, I. Astrand-Grundstrom, B. Strombeck, K. Theilgaard-Monch, K. Anderson, R. Hast, E. Hellstrom-Lindberg, et al. The molecular signature of MDS stem cells supports a stem-cell origin of 5q myelodysplastic syndromes Blood, October 15, 2007; 110(8): 3005 - 3014. [Abstract] [Full Text] [PDF] S. Dupont, A. Masse, C. James, I. Teyssandier, Y. Lecluse, F. Larbret, V. Ugo, P. Saulnier, S. Koscielny, J. P. Le Couedic, et al. The JAK2 617V>F mutation triggers erythropoietin hypersensitivity and terminal erythroid amplification in primary cells from patients with polycythemia vera Blood, August 1, 2007; 110(3): 1013 - 1021. [Abstract] [Full Text] [PDF] A. Tefferi Primary myelofibrosis and its paraneoplastic stromal effects Haematologica, May 1, 2007; 92(5): 577 - 579. [Full Text] [PDF] C. Bogani, P. Guglielmelli, E. Antonioli, A. Pancrazzi, A. Bosi, and A. M. Vannucchi B-, T-, and NK-cell lineage involvement in JAK2V617F-positive patients with idiopathic myelofibrosis Haematologica, February 1, 2007; 92(2): 258 - 259. [Abstract] [Full Text] [PDF] R. Skoda The Genetic Basis of Myeloproliferative Disorders Hematology, January 1, 2007; 2007(1): 1 - 10. [Abstract] [Full Text] [PDF] R. Hoffman and D. Rondelli Biology and Treatment of Primary Myelofibrosis Hematology, January 1, 2007; 2007(1): 346 - 354. [Abstract] [Full Text] [PDF]

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