Clonal dynamics and chemoresistance mechanisms of minimal residual disease in acute leukemia

Project Narrative. Relapsed and refractory pediatric leukemia represents a major clinical challenge as it is almost invariably associated with resistance to standard therapies and the temporal window between relapse and death in refractory cases is short. This leukemia research proposal seeks to establish the specific role of minimal residual disease- and relapse-associated transcriptional and epigenetic regulators as drivers of drug-tolerant persistent phenotypes and chemotherapy resistance. These studies will be impactful to our understanding of the mechanisms conducive to therapeutic failure and will facilitate the rationale design of therapies directed to the eradication of high-risk minimal residual disease and the prevention of leukemia relapse.