While IFNAR1 has not been found mutated or deleted in t(8;21)(q22;q22.1) AML, we could show that BRCC3 mutations render t(8;21)(q22;q22.1) AML cells less sensitive to IFNα-mediated toxicity through impaired deubiquitination and function of IFNAR1. Here, IFNAR1 is linked to acute myeloid leukemia.