Separately, dihydroorotate dehydrogenase (DHODH)—the rate-limiting enzyme in de novo pyrimidine synthesis—acts as a metabolic checkpoint for myeloid differentiation in multiple AML models: selective DHODH inhibition induces differentiation and reduces leukemia-initiating activity, and the effect is fully rescued by exogenous uridine, indicating that the mechanism reflects uridine monophosphate supply restriction rather than off-target effects. Here, DHODH is linked to leukemia.