title: Mutations of SETBP1 and JAK3 in juvenile myelomonocytic leukemia: a report from the Italian AIEOP study group.
abstract: Juvenile myelomonocytic leukemia (JMML) is a rare aggressive disease of early childhood. Driver mutations in the Ras signaling pathways are a key feature of JMML patients. Mutations in SETBP1 and JAK3 were recently identified in a subset of JMML patients characterized by poor prognosis and progression of disease. In this study, we report the results of a screening for mutations in SETBP1 and JAK3 of a cohort of seventy Italian patients with JMML, identifying 11.4% of them harboring secondary mutations in these two genes and discovering two new mutations in the SKI domain of SETBP1.JMML xenotransplantation and colony assay provide an initial understanding of the secondary nature of these events occurring in early precursor cells and suggest a different propagating capacity of clones harboring particular mutations.
authors.affiliation: Department of Women's and Children's Health, Laboratory of Oncohematology, University of Padova, Padova, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bresolin
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: De Filippi
authors.affiliation: Oncologia ed Ematologia Pediatrica "Lalla Seràgnoli", University of Bologna, Ospedale S. Orsola Malpinghi, Bologna, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Vendemini
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Mirko
authors.initials: M
authors.lastname: D'Alia
authors.affiliation: Oncoematologia Pediatrica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione Policlinico San Matteo, Pavia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Zecca
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany.
authors.forename: Lueder H
authors.initials: LH
authors.lastname: Meyer
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Danesino
authors.affiliation: Department of Pediatric Onco-Hematology, IRCCS Ospedale Pediatrico Bambino Gesù, Roma, University of Pavia, Pavia, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: Oncologia ed Ematologia Pediatrica "Lalla Seràgnoli", University of Bologna, Ospedale S. Orsola Malpinghi, Bologna, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Masetti
authors.affiliation: Department of Women's and Children's Health, Laboratory of Oncohematology, University of Padova, Padova, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.affiliation: Department of Women's and Children's Health, Laboratory of Oncohematology, University of Padova, Padova, Italy.
authors.forename: Geertruy
authors.initials: G
authors.lastname: Te Kronnie
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002675:Child, Preschool; D005260:Female; D064593:Heterografts; D006801:Humans; D007558:Italy; D053616:Janus Kinase 3 / Q000235:genetics*; D054429:Leukemia, Myelomonocytic, Juvenile / Q000235:genetics*; D008297:Male; D051379:Mice; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D009687:Nuclear Proteins; C425066:SETBP1 protein, human; C507933:JAK3 protein, human; D053616:Janus Kinase 3
keywords: JAK3; JMML; SETBP1; murine model