Our study identified a long-range Notch and ETS1-bound MYB enhancer as the top-ranked essential element; established the important physiological role of this element in hematopoietic stem cells and early T cell progenitors (ETPs); determined the essential oncogenic role of this element for T cell leukemogenesis; showed the dependence of this element on ETS1 for chromatin accessibility and activity in one T-ALL context; and highlighted SWI/SNF and ETS1 degradation but not Notch inhibition as approaches that might target this element, among multiple other effects. This evidence concerns the gene ETS1 and acute lymphoblastic leukemia.