MLL-ENL initiates AML most efficiently when it is induced in neonates. (A) Overview of the strategy for inducing MLL-ENL at E10.5, P0, and 3 weeks and 8 weeks after birth. (B) Kaplan-Meier survival curves for mice after MLL-ENL induction at the indicated ages. **P < .01, ***P < .0001 relative to induction at 8 weeks after birth. #P < .0001 for P0 relative to E10.5 induction. Survival curves were compared with the log-rank test. Group sizes are indicated. (C) Representative flow plot for AML specimens from Tet-OFF-MLL-ENL mice. (D) Representative AML cytospin. Scale bar indicates 100 μM. (E) Expression of the MLL-ENL transcript by RNA-seq after induction at E10.5. Reads from HPCs and pGMs were mapped to the human MLL-ENL sequence for the indicated induction ages and genotypes. Reads per kilobase of transcript per million mapped reads values from each sample were normalized to one allele of endogenous Mll1.