Leukemia is the most common childhood cancer. While there has been great progress in curing children from leukemia, many children still succumb to this disease. Our ultimate aim is to cure every child with leukemia. Towards this goal we need to understand the basis for drug resistance of the leukemias subtypes that currently are incurable. We plan to use advanced genomic tools, focusing on single cell sequencing, to identify the precise road map of resistant leukemia evolution and to discover novel targets for therapy.