Mechanisms of excessive IRAK1/4 activation may include increasing expression of TLR 9 with subsequent amplification of innate immune pathways in FLT3-ITD AML cells and/or arising genetic mutations within the spliceosome (SF3B1 or U2AF1) which causes constitutive activation of the “myddosome”, leading to NF-kB overactivity and excessive B-cell proliferation, which can cause IRAK-4-L overexpression. This evidence concerns the gene NFKB1 and acute myeloid leukemia.