Mutations of SETBP1 and JAK3 in juvenile myelomonocytic leukemia: a report from the Italian AIEOP study group

// Silvia Bresolin 1 , Paola De Filippi 2 , Francesca Vendemini 3 , Mirko D’Alia 2 , Marco Zecca 4 , Lueder H. Meyer 5 , Cesare Danesino 2 , Franco Locatelli 6 , Riccardo Masetti 3 , Giuseppe Basso 1 , Geertruy te Kronnie 1 1 Department of Women’s and Children’s Health, Laboratory of Oncohematology, University of Padova, Padova, Italy 2 Department of Molecular Medicine, University of Pavia, Pavia, Italy 3 Oncologia ed Ematologia Pediatrica “Lalla Seragnoli”, University of Bologna, Ospedale S. Orsola Malpinghi, Bologna, Italy 4 Oncoematologia Pediatrica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Fondazione Policlinico San Matteo, Pavia, Italy 5 Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center, Ulm, Germany 6 Department of Pediatric Onco-Hematology, IRCCS Ospedale Pediatrico Bambino Gesu, Roma, University of Pavia, Pavia, Italy Correspondence to: Silvia Bresolin, email: silvia.bresolin@unipd.it Keywords: JMML, SETBP1, JAK3, murine model Received: November 27, 2015      Accepted: February 21, 2016      Published: March 09, 2016 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.