GLUL as a novel therapeutic target in pediatric T-ALL

Dr. Daniel Herranz, Ph.D. – Rutgers Biomedical and Health Sciences (Rutgers Health), New Brunswick, NJ

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy that prominently affects kids. Despite recent advances, 20% of children still relapse and the prognosis of these cases remains extremely poor, highlighting the need to discover novel targeted therapeutic approaches. We previously demonstrated the therapeutic effects of targeting metabolic routes in leukemia. In this setting, our latest results have identified a novel metabolic regulator (GLUL) as an important player in T-ALL. Indeed, with genetic tricks by which we can remove GLUL from leukemias in mice, we have observed very significant therapeutic effects, curing 50% of the mice. However, there is nothing known about GLUL in T-ALL. Thus, here we will comprehensively dissect the effects of targeting GLUL in T-ALL using state-of-the-art techniques in human T-ALL cell lines, mouse primary leukemias in vivo and patient-derived xenografts. Integration of mouse and human data will allow us to understand how T-ALL cells respond to GLUL inhibition. Our results will help us design new combinations with current treatments that will result in stronger antileukemic effects and reduced relapses in the future.