People with a third copy of chromosome 21, known as trisomy 21, are at high risk of developing Acute Myeloid Leukaemia (AML), an aggressive form of blood cancer. Scientists led by the Department of Paediatrics at University Hospital Frankfurt have now identified the cause: although the additional chromosome 21 leads to increased gene dosage of many genes, it is above all the perturbation of the RUNX1 gene – a gene that regulates many other genes – that seems to be responsible for AML pathogenesis. Targeting the perturbed regulator could pave the way for new therapies.