SMAD3 and chronic myelogenous leukemia, BCR-ABL1 positive: Collectively, our results indicate that nutrient signalling through a p38MAPK–Smad3 axis that is activated by internalized dipeptide species is essential for CML stem cell activity in vitro and in vivo. Thus, this nutrient supply and its downstream signalling pathway may offer novel candidate therapeutic targets for eradicating CML stem cells.