Long-range enhancers control the expression of MYC in T-ALL. During T-cell development and in the context of T-ALL, NOTCH1 activates MYC expression via interaction of the NMe long-range enhancer with regulatory elements in the MYC promoter. In some T-ALL cell lines, sustained NOTCH1 inhibition with GSIs selects a persistent population in which MYC is reactivated independently of NOTCH via recruitment of a further distal group of enhancers normally active in the myeloid compartment (acute myeloid leukemia or AML enhancer cluster).