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| Home > Publications database > Enhancer hijacking discovery in acute myeloid leukemia by pyjacker identifies MNX1 activation via deletion 7q. |
| Home > Publications database > Enhancer hijacking discovery in acute myeloid leukemia by pyjacker identifies MNX1 activation via deletion 7q. |
| Journal Article | DKFZ-2025-00686 |
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2025
American Association for Cancer Research
Philadelphia, PA
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Please use a persistent id in citations: doi:10.1158/2643-3230.BCD-24-0278
Abstract: Acute myeloid leukemia with complex karyotype (ckAML) is characterized by high genomic complexity, including frequent TP53 mutations and chromothripsis. Genomic rearrangements that reposition active enhancers near proto-oncogenes, leading to their aberrant expression, have not been systematically investigated in AML. To facilitate the discovery of such 'enhancer hijacking' events, we developed pyjacker, a computational tool, and applied it to 39 ckAML samples. Pyjacker identified several enhancer hijacking events in AML patient samples, including aberrant expression of motor neuron and pancreas homeobox 1 (MNX1), which can result from del(7)(q22q36) and is associated with hijacking of a CDK6 enhancer. MNX1 activation occurs in 1.4% of AML patients and shows significant co-occurrence with BCOR mutations. Through a xenograft mouse model, we demonstrated that MNX1 is required for leukemia cell fitness. Pyjacker is an easy-to-use, accurate, and broadly applicable tool for identifying consequences of genomic events driving tumorigenesis, especially when germline genomic data is missing.
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