title: Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia.
abstract: The recurrent t(1;22)(p13;q13) translocation is exclusively associated with infant acute megakaryoblastic leukemia. We have identified the two genes involved in this translocation. Both genes possess related sequences in the Drosophila genome. The chromosome 22 gene (megakaryocytic acute leukemia, MAL) product is predicted to be involved in chromatin organization, and the chromosome 1 gene (one twenty-two, OTT) product is related to the Drosophila split-end (spen) family of proteins. Drosophila genetic experiments identified spen as involved in connecting the Raf and Hox pathways. Because almost all of the sequences and all of the identified domains of both OTT and MAL proteins are included in the predicted fusion protein, the OTT-MAL fusion could aberrantly modulate chromatin organization, Hox differentiation pathways, or extracellular signaling.
authors.affiliation: U434 Institut National de la Santé et de la Recherche Médicale-Centre d'Etude du Polymorphisme Humain (CEPH), 27 Rue J. Dodu, 75010 Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Mercher
authors.forename: M B
authors.initials: MB
authors.lastname: Coniat
authors.forename: R
authors.initials: R
authors.lastname: Monni
authors.forename: M
authors.initials: M
authors.lastname: Mauchauffe
authors.forename: F
authors.initials: F
authors.lastname: Nguyen Khac
authors.forename: L
authors.initials: L
authors.lastname: Gressin
authors.forename: F
authors.initials: F
authors.lastname: Mugneret
authors.forename: T
authors.initials: T
authors.lastname: Leblanc
authors.forename: N
authors.initials: N
authors.lastname: Dastugue
authors.forename: R
authors.initials: R
authors.lastname: Berger
authors.forename: O A
authors.initials: OA
authors.lastname: Bernard
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002878:Chromosomes, Human, Pair 1; D002892:Chromosomes, Human, Pair 22; D004247:DNA; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D007947:Leukemia, Megakaryoblastic, Acute / Q000235:genetics*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D016601:RNA-Binding Proteins; D017386:Sequence Homology, Amino Acid; D014178:Translocation, Genetic
chemical_list: D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D011506:Proteins; C431574:RBM15 protein, human; D016601:RNA-Binding Proteins; C402387:Spen protein, Drosophila; D004247:DNA