Decitabine (DAC) is one of the main drugs used in the treatment of HR-MDS, and DAC alone may be resistant by a mechanism that induces NF-E2-related factor 2 (Nrf2) activation and a downstream antioxidant response that inhibits reactive oxygen species (ROS) generation, leading to drug resistance. Here, NFE2L2 is linked to myelodysplastic syndrome.