Using a chromosome conformation capture-based PCR assay and CRISPR-mediated deletion of a minimal CTCF-binding motif between HOXA7 and HOXA9 (CBS7/9), Luo and colleagues proposed that the CTCF boundary was crucial for higher order chromatin organization by showing the depletion of CBS7/9 disrupted chromatin interactions and significantly reduced HOXA9 transcription in MLLr AML MOLM13 cells with t(9;11) (Luo et al., 2018; Luo et al., 2019). Here, HOXA9 is linked to acute myeloid leukemia.