Epigenomics of High Risk Pediatric T Cell Leukemia

T Cell Acute Lymphoblastic Leukemia (T-ALL) is an aggressive leukemia with increased incidence in children, adolescents and young adults. Currently, the standard treatment of T-ALL patients is intensive chemotherapy with almost 70%, 5-year event free survival for pediatric patients. Moreover, such non-targeted therapies fail to address high-risk T-ALL subtypes, with less than 40% of the patients becoming long-term survivors in the case of one such subtype, the ETP T-ALL (a more immature, stem cell-like flavor of the disease).

Unfortunately, recent attempts to introduce targeted therapies were plagued by both toxicity and resistance, further underlining the urgency and need for new treatments that also target leukemia initiating cells (LIC) to achieve complete disease remission. Recent genetic studies coming from our Team members and other investigators have identified novel oncogenic triggers for this disease and suggested new ways to target it therapeutically.

Project Goal
We test here compounds called BET inhibitors, which we have shown to have anti-T-ALL activity both in vitro and in animal models of the disease. Here we test whether these compounds can also target ETP-ALL and achieve that by studying the mechanism of action and testing drug efficacy using both disease animal models and human ETP-ALL xenografts. These studies will offer the first in depth analysis in high-risk ETP-ALL and study a novel drug, which will be the first therapy option for kids afflicted by this devastating disease.