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Blood, 15 November 2007, Vol. 110, No. 10, pp. 3735-3743. Prepublished online as a Blood First Edition Paper on August 20, 2007; DOI 10.1182/blood-2007-05-089003. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-05-089003v1 110/10/3735    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 Chaligné, R. Articles by Giraudier, S. Search for Related Content PubMed PubMed Citation Articles by Chaligné, R. Articles by Giraudier, S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Evidence for MPL W515L/K mutations in hematopoietic stem cells in primitive myelofibrosis Ronan Chaligné1, Chloé James1,2, Carole Tonetti3, Rodolphe Besancenot1, Jean Pierre Le Couédic1, Fanny Fava1, Fréderic Mazurier2, Isabelle Godin1, Karim Maloum4, Frédéric Larbret1, Yann Lécluse1, William Vainchenker1, and Stéphane Giraudier1,3 1 Institut National de la Santé et de la Recherche Médicale (INSERM), U790, Université Paris XI, Institut Gustave Roussy, Villejuif; 2 INSERM, U876, Université Bordeaux 2, Bordeaux; 3 Assistance Pubpique-Hôpitaux Paris (AP-HP), Laboratoire d'Hématologie, Hôpital Henri Mondor and Université Paris XII, Créteil; and 4 AP-HP, Laboratoire d'Hématologie, Hôpital La Pitié-Salpétrière, Paris, France The MPL (W515L and W515K) mutations have been detected in granulocytes of patients suffering from certain types of primitive myelofibrosis (PMF). It is still unknown whether this molecular event is also present in lymphoid cells and therefore potentially at the hematopoietic stem cell (HSC) level. Toward this goal, we conducted MPL genotyping of mature myeloid and lymphoid cells and of lymphoid/myeloid progenitors isolated from PMF patients carrying the W515 mutations. We detected both MPL mutations in granulocytes, monocytes, and platelets as well as natural killer (NK) cells but not in T cells. B/NK/myeloid and/or NK/myeloid CD34+CD38–-derived clones were found to carry the mutations. Long-term reconstitution of MPL W515 CD34+ cells in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice was successful for as long as 12 weeks after transplantation, indicating that MPL W515 mutations were present in HSCs. Moreover, the 2 MPL mutations induced a spontaneous megakaryocytic growth in culture with an overall normal response to thrombopoietin (TPO). In contrast, erythroid progenitors remained EPO dependent. These results demonstrate that in PMF, the MPL W515L or K mutation induces a spontaneous megakaryocyte (MK) differentiation and occurs in a multipotent HSCs. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Marty, R. Chaligne, C. Lacout, S. N. Constantinescu, W. Vainchenker, and J.-L. Villeval Ligand-independent Thrombopoietin Mutant Receptor Requires Cell Surface Localization for Endogenous Activity J. Biol. Chem., May 1, 2009; 284(18): 11781 - 11791. [Abstract] [Full Text] [PDF] A. M. Vannucchi, P. Guglielmelli, and A. Tefferi Advances in Understanding and Management of Myeloproliferative Neoplasms CA Cancer J Clin, May 1, 2009; 59(3): 171 - 191. [Abstract] [Full Text] [PDF] K. Hussein, O. Bock, K. Theophile, J. Schlue, M. Ballmaier, N. Kroger, G. Gohring, G. Busche, and H. 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Cervantes, F. W. G. Leebeek, C. Marzac, B. Cassinat, S. Chevret, D. Cazals-Hatem, A. Plessier, J.-C. Garcia-Pagan, S. D. Murad, et al. The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis: a report on 241 cases Blood, May 15, 2008; 111(10): 4922 - 4929. [Abstract] [Full Text] [PDF] L. Malcovati and M. Cazzola Myelodysplastic/myeloproliferative disorders Haematologica, January 1, 2008; 93(1): 4 - 6. [Full Text] [PDF]

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