Graphic abstract. Left panel - GPRC5C modulates AML aggression. Middle panel - GPRC5C signals through NF-κB to enhance the expression of SLC7A5 and SLC43A1. Right panel - Inhibition of SLC7A5 with JPH203 targets the respiratory capacity of leukemic cells, hindering their viability. This effect is strengthen by the addition of venetoclax and azacitidine.