Although enhanced NF-κB signaling is associated with myeloid differentiation in normal hematopoiesis and in MLL-AF9 LSCs (Bottero et al., 2006; Eriksson et al., 2017), the NF-κB subunit, v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA) has also been found to sustain an MLL-dependent LSC program (Kuo et al., 2013) and accelerate leukemia development (Xiu et al., 2018). This evidence concerns the gene KMT2A and leukemia.