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Blood, 1 March 2007, Vol. 109, No. 5, pp. 2202-2204. Prepublished online as a Blood First Edition Paper on October 26, 2006; DOI 10.1182/blood-2006-09-045963. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-09-045963v1 109/5/2202    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 Penard-Lacronique, V. Search for Related Content PubMed PubMed Citation Articles by Malinge, S. Articles by Penard-Lacronique, V. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 6, 2006 Accepted October 18, 2006 A novel activating JAK2 mutation in a Down Syndrome patient with B-cell acute lymphoblastic leukemia Sebastien Malinge, Raouf Ben-Abdelali, Catherine Settegrana, Isabelle Radford-Weiss, Marianne Debre, Kheira Beldjord, Elizabeth A Macintyre, Jean-Luc Villeval, William Vainchenker, Roland Berger, Olivier A Bernard, Eric Delabesse, and Virgine Penard-Lacronique* Institute National de la Sante et de la Recherche Scientifique, E0210, Paris, France Hopital Necker-Enfants Malades, Assistance Publique - Hopitaux de Paris, France INSERM, U768, Hopital Necker-Enfants Malades, Paris, France Universite Rene Descartes, Paris, France INSERM, U790, IFR54, Institut Gustave Roussy, Villejuif, France Universite Paris XI, Orsay, France * Corresponding author; email: penard{at}necker.fr. Activation of tyrosine kinase genes is a frequent event in human hematological malignancies. Because gene activation could be associated with gene dysregulation, we attempted to screen for activating gene mutation based on high-level gene expression. We focused our study on the Janus Kinase 2 (JAK2) gene in 90 cases of acute leukemia. This strategy led to the identification of a novel JAK2 acquired mutation in a Down syndrome (DS) patient suffering from B cell precursor acute lymphoblastic leukemia (BCP-ALL). This mutation involves a 5 amino-acids deletion within the JH2 pseudokinase domain (JAK2IREED). Expression of JAK2IREED in Ba/F3 cells induced constitutive activation of the JAK-STAT pathway and growth factor independent cell proliferation. These results highlight the JAK2 pseudokinase domain as an oncogenic hot spot and indicate that activation of the JAK-STAT pathway may contribute to lymphoid malignancies and hematological disorders observed in children with DS. 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