This novel mechanism has two linked features: (1) primitive CML stem cells take up dipeptide species through Slc15A2 transporter activity, and (2) these internalized dipeptides regulate nutrient signalling pathway(s) through p38MAPK-mediated Smad3–Ser208 phosphorylation. This evidence concerns the gene SMAD3 and chronic myelogenous leukemia, BCR-ABL1 positive.