Treatment with Lys05 in combination with AC220 resulted in significantly enhanced inhibition of AML cell growth (p=0.02) and increased induction of apoptosis (p=0.024) compared to AC220 alone. We confirmed that inhibition of autophagy by shRNA-mediated knockdown of the critical autophagy gene ATG5 also enhanced sensitivity of AML cells to AC220 treatment (p=0.004)....autophagy inhibition enhances sensitivity of FLT3-ITD+ AML stem cells to TKI treatment both in vitro and in vivo.