While survival outcomes in pediatric leukemia have improved tremendously in recent years, certain patient groups remain at increased risk for treatment failure and early relapse. While genome sequencing has uncovered the mutations driving pediatric leukemias, this has not yet altered treatments or generated survival benefits. While many researchers focus on studying specific mutations, we propose that targeting proteins that are never mutated in pediatric leukemia may actually be more beneficial (suggesting the cancer cells require this gene for their growth). One such protein is the histone demethylase KDM6B, and we have shown in mice that when we inhibit KDM6B with genetic tools, the growth of pediatric leukemia cells in almost completely blocked. The goals of this study are to use primary cells from pediatric leukemia patient specimens to determine how KDM6B sustains leukemia growth to define how to design new drugs
· Determine if targeting KDM6B in pediatric patient samples inhibits leukemogenesis.
· Identify how KDM6B drives pediatric leukemia to optimize therapeutic targeting.
Potential impact on child health
There are almost no treatments for children with leukemia when chemotherapy is ineffective, or for those who suffer relapse. The goal of this study is to identify new drug targets for pediatric leukemias with particularly poor treatment outcomes.