NFE2L2 and acute lymphoblastic leukemia: These data corroborate the “open” hypothesis that treatment with certain drugs can influence the response to other agents by activating a NRF2-dependent surveillance system and establish a potential AKR1C-mediated drug resistance loop during T-ALL therapy and highlight the relevance of potential pharmacological inhibition of AKR1C1-3 as adjuvant treatment to current chemotherapy protocols.