New Investigator Research Grant Program

We want to better understand the developmental timing and cellular context of the first genetic events that drive the development of pediatric leukemia so that we can identify earlier stages of clinical intervention prior to onset of leukemia. The first genetic alterations in pediatric leukemia often occur during pregnancy, presumably within rare long-lived cells called hematopoietic stem cells (HSC), the cells that are responsible for the lifelong maintenance of the human blood system. Our proposal has the potential to validate that the concept of pre-leukemic HSC holds during fetal blood development and could give precise biological and molecular insight into how this initiation occurs. Children with Down Syndrome (DS) have a 150-fold increased incidence of developing Acute Myeloid Leukemia (AML) by age 4. Our preliminary data suggest that Down Syndrome HSCs express a gene signature consistent with rare ciliopathy diseases. Our project has the potential to identify a new pre-leukemic predisposition for pediatric leukemias, many of which are associated with acquired or congenital chromosome 21 alterations. While this project is focused on trisomy 21, the initiation and progression of myeloid leukemia in DS provides a powerful paradigm for research into other pediatric leukemias that also have their origins in utero.