Resumen
Cancers progress and become resistant to therapies by acquiring novel, unpredictable genomic events. Chronic myeloid leukemia (CML) is a blood cancer characterized by the progression from a chronic phase towards an aggressive acute leukemia called ?blast crisis? due to the accumulation of genomic abnormalities in the genetically unstable leukemic clone. The aim of our work was to reproduce these events using induced pluripotent stem cells (iPSCs) harboring the Philadelphia chromosome. These iPSCs with unlimited proliferation potential can be used to generate large numbers of leukemic cells in vitro. We show here that we can also use them for inducing genomic instability by mutagenesis, giving rise to leukemic cells harboring genomic alterations found in a large cohort of patients in blast crisis. We thus show that this iPSC-based ?blast crisis in a dish? technology could be used for gene discovery and drug targeting strategies in CML and other hematological malignancies.