title: Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia.
abstract: 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.
authors.affiliation: Center for Human Genetics, University of Leuven, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Peeters
authors.forename: S D
authors.initials: SD
authors.lastname: Raynaud
authors.forename: J
authors.initials: J
authors.lastname: Cools
authors.forename: I
authors.initials: I
authors.lastname: Wlodarska
authors.forename: J
authors.initials: J
authors.lastname: Grosgeorge
authors.forename: P
authors.initials: P
authors.lastname: Philip
authors.forename: F
authors.initials: F
authors.lastname: Monpoux
authors.forename: L
authors.initials: L
authors.lastname: Van Rompaey
authors.forename: M
authors.initials: M
authors.lastname: Baens
authors.forename: H
authors.initials: H
authors.lastname: Van den Berghe
authors.forename: P
authors.initials: P
authors.lastname: Marynen
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics* / Q000648:ultrastructure; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics* / Q000648:ultrastructure; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics* / Q000648:ultrastructure; D004273:DNA, Neoplasm / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D009857:Oncogenes; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D014178:Translocation, Genetic / Q000235:genetics*; D053614:Janus Kinase 2; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D004273:DNA, Neoplasm; D015514:Oncogene Proteins, Fusion; C108603:TEL-JAK2 fusion protein, human; D053614:Janus Kinase 2; D000097764:ETS Translocation Variant 6 Protein