LG-362B promoted differentiation in both APL and ATRA-resistant APL cells and in transplantable mouse models with ATRA-sensitive or resistant cells. Administration of 10 mg/kg LG-362B to HL-60 xenografted mice markedly extended survival, likely through caspase-dependent degradation of PML-RARα. Here, PML is linked to acute promyelocytic leukemia.