Expression of ASS1 and ASL is higher in ADI-PEG 20–resistant AML and normal HSCs. The relative expression of ASS1 mRNA (A) and ASL mRNA (B) was significantly higher in ADI-PEG 20–resistant AML (n = 18) than in ADI-PEG 20–sensitive AML (n = 19). ASS1 expression was higher in AML (n = 13) and GMPB (n = 4) after in vitro culture following ADI-PEG 20 exposure compared with control (C). Normal human bone marrow HSCs expressed greater amounts of ASS1 than lymphocytes or other marrow cells (CD34⁻ CD3⁻ CD19⁻) cells (n = 6) (D). (E) The uptake of labeled ¹³C₆ arginine after 10 minutes was greater in sensitive AML (n = 6) than resistant AML (n = 6). The uptake of labeled arginine was significantly reduced by cationic amino acid transporter-1 (CAT-1) inhibitor in sensitive AML cells only. (F) Plasma arginine concentration was measured in patients at diagnosis of AML (n = 15). The arginine concentration was significantly lower than in healthy controls (n = 5). *P < .05.