Acute myeloid leukaemia (AML) is an aggressive cancer of the bone marrow with an overall survival of ~30%. Outcomes for older patients are especially poor, with cure rates of only 10-15%. Treatment for AML has not changed substantially in more than 30 years. Mutations in the cohesin complex occur in 12-15% AML, and evidence shows they are causative of AML. Cohesin brings regulatory elements, known as ‘enhancers’, to genes, to regulate their expression in response to signalling pathways. Wnt signalling, which is also implicated in leukaemia, is altered by cohesin mutation. In this project, we will test two hypotheses: 1. That cohesin mutation and Wnt signalling cooperate to ‘cluster’ enhancers and drive chromosome translocation, leading to AML development. 2. That enhancer-blocking drugs will reverse these effects. The results will identify a new genetic combination as a molecular cause for AML and uncover novel options for therapy.