CDK4-driven ketogenesis rewires histone modification to promote leukemia

How ketogenic metabolites affect tumorigenesis, and whether ketone metabolism becomes deregulated in cancer cells, remain incompletely understood. Using T-cell acute lymphoblastic leukemia (T-ALL) as a model, we demonstrate that the ketone body β-hydroxybutyrate (BHB) is elevated in cancer cells and exerts a strong pro-leukemogenic effect. Remarkably, the key ketogenic enzyme β-hydroxybutyrate dehydrogenase 1 (BDH1) is significantly upregulated, enabling carbohydrate-driven BHB synthesis in leukemia cells.