Translocation t(6;7) in AML-M4 cell line GDM-1 results in MNX1 activation through enhancer-hijacking

The leukemic cell line GDM-1 was established from a patient with acute myelomonoblastic leukemia. GDM-1 cells carry a reciprocal translocation t(6;7)(q23;q36) juxtaposing the transcription factor (TF) gene motor neuron and pancreas homeobox 1 (MNX1, also designated HLXB9 or HB9) on chromosome 7 (chr7) to the locus of the transcriptional activator MYB on chr6. The translocation does not result in a fusion transcript but leads to aberrant activation of MNX1, suspected to be due to altered topologically associating domains, nuclear positioning or ectopic mechanisms. GDM-1 represents the only AML cell line overexpressing MNX1. Here we demonstrate that the interaction between the MNX1 promoter with a 'hijacked' enhancer from the MYB/AHI1 locus leads to ectopic activation of MNX1.