title: Activating mutations in human acute megakaryoblastic leukemia.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Scientifique (INSERM), E0210, Paris, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Malinge
authors.forename: Christine
authors.initials: C
authors.lastname: Ragu
authors.forename: Veronique
authors.initials: V
authors.lastname: Della-Valle
authors.forename: Didier
authors.initials: D
authors.lastname: Pisani
authors.forename: Stefan N
authors.initials: SN
authors.lastname: Constantinescu
authors.forename: Christelle
authors.initials: C
authors.lastname: Perez
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Villeval
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhardt
authors.forename: Judith
authors.initials: J
authors.lastname: Landman-Parker
authors.forename: Lucienne
authors.initials: L
authors.lastname: Michaux
authors.forename: Nicole
authors.initials: N
authors.lastname: Dastugue
authors.forename: André
authors.initials: A
authors.lastname: Baruchel
authors.forename: William
authors.initials: W
authors.lastname: Vainchenker
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bourquin
authors.forename: Virginie
authors.initials: V
authors.lastname: Penard-Lacronique
authors.forename: Olivier A
authors.initials: OA
authors.lastname: Bernard