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Raynaud, Jan Cools, Iwona Wlodarska, Josiane Grosgeorge, Patrick Philip, Fabrice Monpoux, Luc Van Rompaey, Mathijs Baens, Herman Van den Berghe, and Peter Marynen From the Center for Human Genetics, Flanders Interuniversity Institute for Biotechnology, University of Leuven, Leuven, Belgium; Laboratoire de Génétique, Faculté de Médecine, Nice; UEFCT, Hôpital Pasteur, Nice; and Service de Pédiatrie, Hôpital de l'Archet, Nice, France. Translocations in hematologic disease of myeloid or lymphoid origin with breakpoints at chromosome band 12p13 frequently result in rearrangements of the Ets variant gene 6 (ETV6). As a consequence either the ETS DNA-binding domain or the Helix-Loop-Helix (HLH) oligomerization domain of ETV6 is fused to different partner genes. We show here that a t(9; 12)(p24; p13) in a case of early pre-B acute lymphoid leukemia and a t(9; 15; 12)(p24; q15; p13) in atypical chronic myelogenous leukemia in transformation involve the ETV6 gene at 12p13 and the JAK2 gene at 9p24. In each case different fusion mRNAs were found, with only one resulting in an open reading frame for a chimeric protein consisting of the HLH oligomerization domain of ETV6 and the protein tyrosine kinase (PTK) domain of JAK2. The cloning of the complete human JAK2 coding and genomic sequences and of the genomic junction fragments of the translocations allowed a characterization of the different splice events leading to the various mRNAs. JAK2 plays a central role in non-protein tyrosine kinase receptor signaling pathways, which could explain its involvement in malignancies of different hematologic lineages. Besides hop in Drosophila no member of the JAK family has yet been implicated in tumorigenesis. Blood, Vol. 90 No. 7 (October 1), 1997: pp. 2535-2540 © 1997 by The American Society of Hematology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: CYT997: a novel orally active tubulin polymerization inhibitor with potent cytotoxic and vascular disrupting activity in vitro and in vivo Mol. Cancer Ther., November 1, 2009; 8(11): 3036 - 3045. M B K Lambros, D S P Tan, R L Jones, R Vatcheva, K Savage, N Tamber, K Fenwick, A Mackay, A Ashworth, and J S Reis-Filho Genomic profile of a secretory breast cancer with an ETV6-NTRK3 duplication J. Clin. Pathol., July 1, 2009; 62(7): 604 - 612. [Abstract] [Full Text] [PDF] S. Chiaretti and R. Foa T-cell acute lymphoblastic leukemia Haematologica, February 1, 2009; 94(2): 160 - 162. [Full Text] [PDF] R. Burger, S. Le Gouill, Y.-T. Tai, R. Shringarpure, P. Tassone, P. Neri, K. Podar, L. Catley, T. Hideshima, D. Chauhan, et al. 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