FLT3 and acute myeloid leukemia: Importantly, the p21 down-regulation resulting from FLT3-ITD inhibition by AC220 accelerated proliferation and development of FLT3-ITD+ cells that were refractory to AC220, suggesting that treatments targeting FLT3-ITD can eradicate growth-inhibitory signals by inhibiting p21 expression, thereby potentially contributing to FLT3-ITD+ AML progression (Fig 10B & 10C).