Identifying Therapeutic Targets to Prevent Progression of Familial RUNX1 Disorder to AML Using Novel iPSC Models
Background
Children with familial RUNX1 disorder have a high risk of developing leukemia, which in most cases is hard to treat with current chemotherapy. Finding ways to prevent progression of leukemia is the most promising strategy towards the effective management of this disorder.
Project Goals
We propose to develop a novel model of leukemia progression from familial RUNX1 disorder using cutting-edge technologies from the fields of stem cell research and genetic engineering. My laboratory has extensive expertise in developing stem cell models of human disease and has pioneered the study of leukemia with stem cell models, in particular induced pluripotent stem cells (iPSCs). We propose to use the new models that we will develop to recapitulate leukemia progression “in-a-dish” and study the changes that occur upon transformation.
These studies can pinpoint the biological processes that are key to leukemia progression in these patients and need to be targeted therapeutically. They can also provide a new experimental platform to test candidate drugs in a more disease-relevant context and prioritize the most promising drugs for clinical testing. Thus the proposed work can open new avenues for early detection, prevention and therapeutic intervention for children with familial RUNX1 disorder.
