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Therapeutic inhibition of macroautophagy/autophagy is expected to increase chemosensitivity of cancers and alter tumor-stroma interdependence. The hypoxic, metabolically challenged bone marrow microenvironment confers chemoresistance to leukemia cells. The impact of autophagy inhibition in the context of microenvironment-mediated resistance in leukemia is less explored. Our recent studies demonstrated that co-culture of acute myelogenous leukemia (AML) cells with marrow-derived mesenchymal stromal cells (MSC) induces autophagy in AML cells and increases resistance to genotoxic agents (cytarabine and idarubicin). Genetic silencing of ATG7 in AML enhances the sensitivity to these genotoxic agents, an effect that was more pronounced with concomitant silencing of ATG7 in AML and MSCs. Mechanistically, the increased sensitivity of AML cells to genotoxic agents is associated with alteration of …