In summary, our ex vivo data suggest that targeting NFKB2-MIF/CXCLs-CXCR2 pathways including GILT+NFKB-I and/or CXCR2-I (disrupting the internalization/ maintenance of NFKB’s activation) might be a novel therapeutic approach to treat both newly diagnosed and refractory FLT3mut AML patients by effectively suppressing the release of tumor-promoting cytokines to overcome TKI-resistance and prevent AML relapse. Here, CXCR2 is linked to acute myeloid leukemia.