Paradoxically, when MYC was defined to juxtapose both proximal and distal enhancers in myeloid leukemia K562 and WEHI231 B-cell lymphoma (62), ectopic expression of CTCF led to downregulation of MYC, growth retardation and promotion of differentiation into the erythroid lineage (25,26) underscoring the complexity of CTCF’s regulation of MYC across tissue types. The gene discussed is CTCF; the disease is myeloid leukemia.