Depiction of two different mouse models of pediatric (A) and adult (B) Flt3-ITD co-mutant myeloid leukemia. (A) Flt3-ITD plus NUP98-translocation (NUP98-t) leads to early transcriptional reprogramming with unique upregulation of type 1 interferon. Co-mutant MPPs expand to give rise to AML. (B) Flt3-ITD plus RUNX1^MUT leads to late transcriptional reprogramming and expansion of co-mutant MPPs and GMPs giving rise to AML. Professional illustration by Patrick Lane, ScEYEnce Studios.