Role of DNA repair, ROS and apoptosis in daunorubicin chemotherapy of leukaemia

Daunorubicin has been used for nearly 50 years to treat acute leukaemias. Over this time there has been extensive research into its mechanism of action and associated toxicities. Proposed mechanisms of action have included topoisomerase inhibition, reactive oxygen species (ROS) generation and the formation of DNA adducts. Recent discoveries regarding the interaction between ROS and ATM, an initiator of DNA repair and an activator of both p53 and CHK2 with implications for cell cycle arrest and apoptosis, offer intriguing new insights into these mechanisms. We examine the fundamental mechanism of cell kill by anthracyclines in acute leukemia models and correlate mutations in ATM found in acute leukaemia to susceptibility to treatment with anthracyclines.