Leukemogenic blocks to PU.1-mediated myeloid differentiation. Two blocks to the pathway are shown: by the PML-RARA fusion gene product in human APL and by reduced function of PU.1 itself in knockdown or radiation-induced mouse acute myeloid leukemia (AML). The dashed line indicates degradation of PML-RARA, possibly induced by PU.1. Illustration by Kenneth Xavier Probst.