In patients who have been previously treated with ATO, at relapse, about one‐third harbor mutations in the PML‐RARA fusion gene and the clinical outcomes in this subset are poor.19 Besides the mutations in PML‐RARA fusion gene, microenvironment‐mediated drug resistance (EM‐DR) to ATO mediated by the upregulation of the NF‐κB pathway also contributes to drug resistance in relapsed APL.20 Recently, in a mouse model experiment, we showed that this EM‐DR could be overcome by proteasome inhibition.21 The gene discussed is NFKB1; the disease is acute promyelocytic leukemia.