Acute myeloid leukemia results from the accumulation of mutations that deregulate survival and differentiation of hematopoietic cells, and drive leukemia. We have studied the mechanism of leukemia development with oncogenic Ras and CBF mutations for over 20 years. In this application we are proposing studies in mice and leukemic cells to test the role of BIM inhibition as a target for leukemia, and to test RAS inhibitors as candidate therapies for these leukemias. These studies aim at establishing improved targeted therapies in childhood leukemia