Project Grant R01CA289045

The National Cancer Institute awarded a 5-year, $500,719 Project Grant (R01CA289045) to the Regents of the University of Michigan under the Cancer Biology Research program (CFDA 93.396) to study the role of repeat enhancers in driving genetic subtypes of B-cell acute lymphoblastic leukemia (B-ALL) with ETV6 gene aberrations. The research aims to provide direct evidence that activation of GGAA repeat enhancers is the causative mechanism for the gene expression signature of the rare but aggressive ETV6-RUNX1-like B-ALL subtype. Key objectives include investigating the activating mechanisms of GGAA repeat enhancers, their effects on leukemia fitness, and the epigenetic barriers to de novo repeat enhancer activation. The project will also use a proteomic approach to identify factors that cooperate with ETV6 loss to directly activate GGAA repeat enhancers in B-ALL. Insights gained could lead to new therapeutic and preventive strategies for this common childhood cancer.