NOTCH1 and acute lymphoblastic leukemia: However, in T-ALL patients that harbor loss-of-function PHF6 mutations, there is a significant association with activating mutations in NOTCH1 or its downstream target IL7R (Wang et al., 2011; Vicente et al., 2015; Li et al., 2016), indicating that reduced PHF6 function triggers the cells to compensate for the reduced activity of these critical T-lineage proliferation/survival pathways.