Although cases of PU.1 and Upstream Regulatory Element mutations have been recorded in human AML, they are much rarer than in mice.23, 24, 25, 26, 27 Better described are mechanisms suppressing PU.1 function, such as disruption of PU.1 transactivation activity by RUNX1-ETO,11 or interference with PU.1 binding (including at its own promoter site) by PML-RARA.28 Importantly, there has as yet been no specific investigation into the transcriptional programmes associated with the loss of PU.1 activity in AML. Here, RUNX1T1 is linked to acute myeloid leukemia.