Identifying Therapeutic Targets to Prevent Progression of Familial RUNX1 Disorder to AML Using Novel iPSC Models
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.
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.
Project Update (April 2019)
When Eirini Papapetrou, MD, PhD from the Icahn School of Medicine at Mount Sinai started her lab, she devoted her research to developing iPSC models.
This might not mean a lot to those of us who are not researchers. But these models—made from patient-derived cells—could be the key to understanding the drivers behind certain types of acute myeloid leukemia (AML), one of the most difficult and deadliest types of pediatric leuke-mia.
The development of iPSC models is challenging—so challenging that several years ago, none of these models existed. For the past 7 years, Dr. Papapetrou, who is funded through the ALSF partnership with the Babich Foundation, developed sustainable models that she is using to study the RUNX1 mutation. This particular mutation is an inherited platelet disorder with a predisposi-tion to certain types of blood malignancies, including AML.
We interviewed Dr. Papapetrou on the ALSF blog about her RUNX1 research as well as her sci-entific career. Read more here.