The aim of the National Cancer Institute supported Therapeutically Applicable Research to Generate Effective Treatments (TARGET) Initiative is to use next generation sequencing tools to develop new, more effective treatments for childhood cancers including pediatric acute myeloid leukemia (AML). The genetic changes that drive leukemia cells are different in children and adults, therefore, it's important to study pediatric cancers separately.
Preliminary results from TARGET identified multiple patients with a variety of mutations in the ETV6 gene. The aim of my work is to characterize the scope of ETV6 mutations in pediatric AML. In my preliminary studies, I found ETV6 mutations in 6% of pediatric AML. Patients with ETV6 mutations were more likely to have a poor outcome. In addition to mutations, TARGET identified 19 patients with deletions of either a large portion or the entire ETV6 gene. Half of patients with ETV6 deletions also had another marker (CBF) in their leukemia cells that predicts a good response to therapy. However, nearly all patients with a deletion of ETV6 in addition to CBF eventually relapsed. Researchers have been searching for a marker to help predict which patients with CBF AML will relapse and ETV6 may be that marker. The significance of these findings is that ETV6 may be a marker to predict which patients will fail conventional therapy. The hope is that in future clinical trials, we can evaluate if patients who have genetic changes of ETV6 in their leukemia cells will benefit from altered therapy.