Arsenic in leukemia: A RSKy business

It has been known for many years that arsenic trioxide (As(2)O(3); ATO) is an effective therapy for acute promyelocytic leukemia but has little activity against other forms of the disease. ATO has diverse modes of action, but is well known to generate high levels of reactive oxygen species in cells which are believed to be causal in many of its biologic actions.(1) ROS can both activate and suppress signaling through multiple intracellular pathways based on the amount and duration of ROS production.(2) As the basal activity of the MEK1/2-ERK1/2 pathway is often high in acute myeloid leukemias, and that ATO is known to stimulate MEK1/2-ERK1/2 signaling in leukemia, the authors investigated whether knock down of the downstream effector of ERK1/2, RSK1, could enhance the anti-leukemic activity of ATO.(3)(,)(4)