DHODH come un tallone d'Achille metabolico targetabile per il B-ALL resistentente alla chemioterapia.

Relapse remains a major barrier to survival in B-cell acute lymphoblastic leukemia (B-ALL). Both activation of B-cell signaling pathways and increased glucose consumption have been linked to chemoresistance and relapse risk. In this study, we connect these observations by showing that B-ALL cells with active mTOR signaling, marked by high phosphorylated ribosomal protein S6 (pS6+), are glucose dependent. Isotope tracing confirms that pS6+ cells are highly glycolytic and rely on glucose for de novo nucleotide synthesis. Uridine, but not other purines or pyrimidines, rescue pS6+ cells from glucose deprivation, highlighting uridine as essential for survival. Active mammalian target of rapamycin