NB4 cells treated with all-trans retinoic acid generate toxic reactive oxygen species that cause endothelial hyperpermeability

Retinoic acid syndrome (RAS) is a serious complication during induction therapy with all-trans retinoic acid (RA) in patients with acute promyelocytic leukemia. In this study, we examined whether reactive oxygen species (ROS) were involved in capillary leak phenomenon in RAS, using NB4 cells. When cells were stimulated by phorbol 12-myristate 13-acetate, RA-treated cells with matured myeloperoxidase produced toxic ROS, such as singlet oxygen, hypochlorous acid and hydroxyl radical, and brought about endothelial hyperpermeability. Leukemic cells from a patient also produced toxic ROS. These findings indicated that toxic ROS contribute to the development of capillary leak phenomenon in RAS.