Final Report Summary - MOLTALL (Molecularly targeted therapy for T cell acute lymphoblastic leukemia)
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive leukemia that is most common in children and young adolescents. The treatment of this cancer has significantly improved over the last 30 years, and now more than 80 % of children with T-ALL survive, but suffer short and long term severe side effects. In order to improve treatment and make it less toxic, new targets for treatment will be needed. In this project, we have initiated a full genomic characterization of T-ALL with the aim to identify new targets for therapy, and we have generated cell-based and mouse models to verify the oncogenic properties of newly identified oncogenes. Our work shows that PTPN2, PTPRC, RPL5 and CNOT3 are new tumor suppressor genes in T-ALL. In addition, we identified JAK3, IL7R, RPL10 as new oncogenes, and have characterized the spectrum of mutations present in T-ALL using recently developed sequencing technologies. These data reveal the presence of new oncogenic pathways that are implicated in the development and progression of T-ALL, and indicate that JAK kinase inhibitors (targeting JAK3 or IL7R mutants) may be interesting new drugs to be tested for the treatment of T-ALL.