Given the central role of NOTCH1 and MYC in the pathogenesis of T-ALL and the necessity of CD44 and its variant CD44v8–10 for LICs to retain their ‘stemness’ by maintaining a state of low ROS levels, we report here our work with BRD4 degrader in patient-derived xenograft (PDX) and genetic models of T-ALL. The gene discussed is BRD4; the disease is acute lymphoblastic leukemia.