Arginine deprivation using pegylated arginine deiminase has activity against primary acute myeloid leukemia cells in vivo

摘要: The strategy of enzymatic degradation amino acids to deprive malignant cells important nutrients is an established component induction therapy acute lymphoblastic leukemia. Here we show that myeloid leukemia (AML) from most patients with AML are deficient in a critical enzyme required for arginine synthesis, argininosuccinate synthetase-1 (ASS1). Thus, these ASS1-deficient dependent on importing extracellular arginine. We therefore investigated the effect plasma deprivation using pegylated deiminase (ADI-PEG 20) against primary AMLs xenograft model and vitro. ADI-PEG 20 alone induced responses 19 38 vitro 3 6 vivo, leading caspase activation sensitive AMLs. 20–resistant showed higher relative expression ASS1 than This suggests resistant survive by producing through this metabolic pathway could be used as biomarker response. Sensitive more avid uptake environment consistent their auxotrophy combination cytarabine chemotherapy was effective either treatment resulting tested vivo. Our data reasonable paves way clinical trials.