Obiettivo Infant pro-B acute lymphoblastic leukemia (ALL) carrying the fusion oncogene MLL-AF4 is associated with very brief latency and dismal prognosis. Recent studies have revealed an in utero origin of MLL-AF4 but the nature of the target cell for transformation in the embryo/fetus is unknown. Because of the mixed phenotype and the presence of MLL-AF4 in both lymphoid and myeloid lineages, hematopoietic stem/progenitor cells (HSPCs) are likely targets for transformation. The absence of bona fide disease models reflects our very poor understanding of the etiology, pathogenesis, cell of origin and secondary oncogenic events of this leukemia. Here it is proposed to create a murine model for infant MLL-AF4+ pro-B ALL using lentiviral transduction of MLL-AF4 or AF4-MLL in HSPCs at different developmental stages: aorta-gonad-mesonephros (AGM), fetal liver (FL) and neonatal BM. These HSCs can be harvested from a novel BAC transgenic reporter mouse model that based on Vwf-EGFP expression divides multipotent adult HSCs, homogeneous by thus far characterized phenotypes, into two prospectively isolatable subsets: vWF+ HSCs (with platelet/myeloid-biased output) and vWF− HSCs (with lymphoid-biased output). Here, primary lymphoid-biased vWF− HSCs will be used to stably express the oncoproteins and then injected into lethally irradiated hosts. For the first time, we will exploit a model that deciphers HSC heterogeneity to study the transformation capacity of leukemogenic oncoproteins in a specific HSC subset. Campo scientifico medical and health sciencesclinical medicineoncologyleukemiamedical and health sciencesclinical medicineembryology Programma(i) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) FP7-PEOPLE-2013-CIG - Marie-Curie Action: "Career Integration Grants" Invito a presentare proposte FP7-PEOPLE-2013-CIG Vedi altri progetti per questo bando Meccanismo di finanziamento MC-CIG - Support for training and career development of researcher (CIG) Coordinatore FUNDACION PARA LA INVESTIGACION DEL HOSPITAL UNIVERSITARIO LA FE DE LA COMUNIDAD VALENCIANA Contributo UE € 37 500,00 Indirizzo AV FERNANDO ABRIL MARTORELL 106 46026 Valencia Spagna Mostra sulla mappa Regione Este Comunitat Valenciana Valencia/València Tipo di attività Research Organisations Contatto amministrativo Ana Blanco Sanchez (Dr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato Partecipanti (1) Classifica in ordine alfabetico Classifica per Contributo UE Espandi tutto Riduci tutto FUNDACIO INSTITUT DE RECERCA CONTRA LA LEUCEMIA JOSEP CARRERAS Partecipazione conclusa Spagna Contributo UE € 62 500,00 Indirizzo CARRETERA DE CAN RUTI CAMI DE LES ESCOLES S/N 08916 Badalona Mostra sulla mappa Regione Este Cataluña Barcelona Tipo di attività Research Organisations Contatto amministrativo óscar Fraile Sierra (Mr.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato