Activation of a promyelocytic leukemia–tumor protein 53 axis underlies acute promyelocytic leukemia cure

Retinoic acid and arsenic therapies have shown considerable efficacy in patients with acute promyelocytic leukemia, but their exact mechanism of action remains unclear. Here, Hugues de Thé and colleagues uncover a therapeutic effect mediated by nuclear body reformation and p53 activation that involves the induction of a senescence transcriptional program. These data suggest that redifferentiation and apoptosis induction may not be sufficient for the effect of these agents in patients and uncover alternative therapeutic routes that could be applied to other tumor and treatment types.