A working model for the role of STAT5 in regulating RAC1 activity and ROS production in FLT3/ITD-positive AML cells. FLT3/ITD signaling leads to phosphorylation of STAT5 and its subsequent translocation to the nucleus, and helps in cell survival. Our results suggest that RAC1-GTP binding to pSTAT5 is increased in FL3/ITD cells. Both RAC1 and STAT5 appear important for ROS production. Active RAC1 binding to gp91^phox of the NADPH oxidase complex is required for ROS production. Inhibition of FLT3/ITD by CEP-701 leads to the inhibition of STAT5 phosphorylation, decreased RAC1 activity and binding to gp91^phox, and decreased ROS levels. Further investigation is needed to clarify the STAT5/RAC1 interaction at the molecular level.