Studies with knock-in (KI) mice (generated by gene targeting) that carry either the human GFI136N variant allele or the more common human GFI136S allele at the endogenous murine Gfi1 locus (13) provided more insight into the mechanism underlying the association of GFI1 with MDS and AML. The gene discussed is GFI1; the disease is acute myeloid leukemia.