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Blood, 15 November 2008, Vol. 112, No. 10, pp. 4220-4226. Prepublished online as a Blood First Edition Paper on August 28, 2008; DOI 10.1182/blood-2008-01-136366. This Article Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2008-01-136366v1 112/10/4220    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 Malinge, S. Articles by Bernard, O. A Search for Related Content PubMed PubMed Citation Articles by Malinge, S. Articles by Bernard, O. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 28, 2008 Accepted July 21, 2008 Activating mutations in human acute megakaryoblastic leukemia Sebastien Malinge, Christine Ragu, Veronique Della-Valle, Didier Pisani, Stefan N Constantinescu, Christelle Perez, Jean-Luc Villeval, Dirk Reinhardt, Judith Landman-Parker, Lucienne Michaux, Nicole Dastugue, Andre Baruchel, William Vainchenker, Jean-Pierre Bourquin, Virginie Penard-Lacronique*, and Olivier A Bernard INSERM, E0210, Paris, France Universite Rene Descartes, Paris, France INSERM, U790, IFR54, Institut Gustave Roussy, Villejuif, France Ludwig Institute for Cancer Research, Universite catholique de Louvain, Brussels, Belgium Universite Paris XI, Orsay, France Medizinische Hochschule Hannover, Hannover, Germany Service d'hematologie et d'oncologie pediatrique Hopital d'Enfant Armand Trousseau, AP-HP, Paris, France Cliniques Universitaires St Luc, Brussels, Belgium Laboratoire d’Hematologie, Genetique des Hemopathies, Hopital Purpan, Toulouse, France Service d'hematologie pediatrique Hopital St Louis, AP-HP, Paris, France Division of Oncology, Universitaets-Kinderklinik Zurich, Zurich, Switzerland * Corresponding author; email: virginie.penard-lacronique{at}inserm.fr. Oncogenic activation of tyrosine kinase signaling pathway is recurrent in human leukemia. To gain insight into the oncogenic process leading to acute megakaryoblastic leukemia (AMKL) we performed sequence analyses of a subset of oncogenes known to be activated in human myeloid and myeloproliferative disorders. In a series of human AMKL samples from both Down Syndrome and non-Down Syndrome patients, mutations were identified within KIT, FLT3, JAK2, JAK3 and MPL genes with a higher frequency in DS than in non-DS patients. The novel mutations were analyzed using BaF3 cells, showing that JAK3 mutations were activating mutations. Finally, we report a novel constitutively active MPL mutant, MPLT487A, observed in a non-Down Syndrome childhood AMKL that induces a myeloproliferative disease in mouse bone marrow transplantation assay. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Edwards, C. Xie, K. M. LaFiura, A. A. Dombkowski, S. A. Buck, J. L. Boerner, J. W. Taub, L. H. Matherly, and Y. Ge RUNX1 regulates phosphoinositide 3-kinase/AKT pathway: role in chemotherapy sensitivity in acute megakaryocytic leukemia Blood, September 24, 2009; 114(13): 2744 - 2752. [Abstract] [Full Text] [PDF] F. K. Wiseman, K. A. Alford, V. L.J. Tybulewicz, and E. M.C. Fisher Down syndrome--recent progress and future prospects Hum. Mol. Genet., April 15, 2009; 18(R1): R75 - R83. [Abstract] [Full Text] [PDF] S. Malinge, S. Izraeli, and J. D. Crispino Insights into the manifestations, outcomes, and mechanisms of leukemogenesis in Down syndrome Blood, March 19, 2009; 113(12): 2619 - 2628. [Abstract] [Full Text] [PDF] K. R. Rabin and J. A. Whitlock Malignancy in Children with Trisomy 21 Oncologist, February 1, 2009; 14(2): 164 - 173. [Abstract] [Full Text] [PDF]

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