Translating genomic discoveries into improved clinical decision making, mechanistic understanding, and therapy of acute leukemia

The overall objectives of this proposal are to improve clinical decision making of acute leukemia by using integrative genomic sequencing approaches, to increase our understanding of how genetic abnormalities cause acute leukemia, and to identify new cell surface markers on acute leukemia stem cells that can be used as therapeutic targetsIn the first project, new and clinically important genetic changes will be identified prospectively in acute leukemia using different high-throughput sequencing technologies and key findings will be translated into improved clinical decision making.

In the second project, newly identified genetic changes will be functionally studied to delineate mechanisms underlying leukemia development.

The third project is focused on identifying targets affecting leukemia stem cells and on providing in vivo proof-of-concept data for targeted therapies with a focus on antibody-based strategies.Using an integrative sequencing approach to molecularly dissect acute leukemia, we aim to significantly improve the way acute leukemia is understood at the molecular level and diagnosed.

Through functional studies of selected driver mutations, we will increase the mechanistic understanding of how such alterations cause acute leukemia.

Finally, by matching the underlying molecular phenotype of acute leukemia with target identification on the malignant stem cells, we hope to accelerate the development of new antibody-based therapeutics.