“The role of SIRT1 in the pathogenesis and treatment of T-Cell Acute Lymphoblastic Leukemia”
T-Cell Acute Lymphoblastic Leukemia (T-ALL) is an aggressive blood cancer where 20-50% of patients relapse, and there are few therapeutic options at this stage. Notch1 activating mutations are the main driver in T-ALL. However, responses observed with targeted therapies against NOTCH1 have been limited, such that the identification of novel targets and combination therapies is one of the most urgent goals in T-ALL. In this context, we have identified Sirt1 as a critical mediator of resistance to NOTCH1 inhibition. Thus, we propose to dissect the role of Sirt1 in the pathogenesis of T-ALL and as a therapeutic target in vivo.