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CTCF-dependent enhancer hijacking by the EVI1 oncogene in leukemia

Chromosomal rearrangements are a frequent cause of oncogene deregulation in human malignancies. Overexpression of EVI1 is found in a subgroup of acute myeloid leukemia (AML) with 3q26 chromosomal rearrangements which are often therapy resistant. In a cohort of primary t(3;8)(q26;q24) AML samples we observed the translocation of a MYC super-enhancer to EVI1. We generated a patient-based t(3;8)(q26;q24) model in vitro using CRISPR-Cas9 technology and demonstrated hyper-activation of EVI1 by the hijacked MYC super-enhancer. One MYC super-enhancer element in particular, which recruits early hematopoietic regulators, is critical for EVI1 expression and enhancer-promoter interaction. This interaction is facilitated by a CTCF-bound motif upstream of the EVI1 promoter that acts as an enhancer-docking site in t(3;8) AML. Genomic analyses of 3q26-rearranged AML samples point to a common mechanism by which EVI1 uses this CTCF-bound enhancer-docking site to hijack early hematopoietic enhancers.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001006817 Illumina HiSeq 2500 21
EGAD00001006818 Illumina HiSeq 2500 1
EGAD00001006819 Illumina HiSeq 2500 Illumina NovaSeq 6000 13
EGAD00001006820 Illumina HiSeq 2500 28
EGAD00001007910 Illumina HiSeq 2500 Illumina NovaSeq 6000 5
Publications Citations
The leukemic oncogene EVI1 hijacks a MYC super-enhancer by CTCF-facilitated loops.
Nat Commun 12: 2021 5679