Comparison of gene expression profiling among shRNAs-mediated RUNX1 knockdown in MV4-11 cells with various knockdown efficacies

The primary function of RUNX1 in leukemogenesis has been controversial since classical understanding of RUNX1 as an oncosuppressor was challenged by our recent discovery of novel oncogenic features of RUNX1. Here we provide insight into the dual function of RUNX1 through determining the significance of total RUNX expressions in AML cells. Our data indicate that moderately attenuated RUNX1 expression induces increased total RUNX expressions, which subsequently enhances proliferation of AML cells via GSTA2-mediated intracellular ROS removal. Indeed, inhibiting GSTA2 function in vivo prolonged the overall survival period of mice xeno-transplanted with human AML cells. These findings suggest that modulation of RUNX-GST-ROS axis could potentially be a novel therapeutic target in the poorest-prognostic AML patients with intermediate RUNX1 expression levels. MV4-11 cells were transduced with series of shRNAs targeting RUNX1 at various efficacies (Moderate knockdown; MV4-11_sh_Rx1_moderate, Profound knockdown; MV4-11_sh_Rx1_profound_#1 and #2). Control shRNA targets luciferase sequence (sh_Luc.).