SOD2 activation by Foxo suppresses generation of AML1-ETO–induced precursors. (A) Activation of SOD2 or Catalase or Foxo, or inactivation of Akt1 causes suppression of AML1-ETO–mediated hemocyte proliferation. Corresponding UAS constructs (indicated on x-axis) were expressed in hemocytes expressing AML1-ETO (hml^Δ-Gal4,UAS-GFP;UAS-AML1-ETO: hml > AML1-ETO). Number of hemocytes in AML1-ETO mutant was significantly reduced by ectopic expression of Foxo, Akt^dsRNA, SOD2, or Catalase (n = 10, P < .001). Number of hemocytes in AML1-ETO mutant was not significantly affected by overexpression of Akt1, pten^dsRNA, SOD2^dsRNA. hml^Δ-Gal4,UAS-GFP heterozygous were used as wild-type control (WT control). (B) In a wild-type background, the number of hemocytes is not significantly affected by overexpression of SOD2 or Foxo with hml^Δ-Gal4,UAS-GFP. (C) Activation of SOD2 or Foxo causes significant reduction of Wg⁺ hemocyte precursors in AML1-ETO mutant. SOD2 or Foxo were expressed in hemocytes expressing AML1-ETO (hml > AML1-ETO). Scale bars, 5 μm. (D) A schematic diagram depicting the relationship between PI3K/Akt and EcR-B1 pathways in negative regulation of FoxO that is required for positive regulation of ROS-inactivating enzymes. We propose that AML1-ETO suppresses FoxO function, leading to an increase of ROS in hemocyte precursors.