By interrogating the 3D genome organization of primary human leukaemia specimens, Kloetgen revealed widespread differences in intra-TAD chromatin interactions and TAD boundary insulation and specifically identified a TAD “fusion” event linked to the absence of CTCF-mediated insulation that enabled direct interaction between the MYC promoter and a distal super-enhancer [81]. The gene discussed is MYC; the disease is leukemia.