AML blasts are auxotrophic for arginine. (A) AML patients’ blasts and AML cell lines were cultured in complete or arginine-depleted media. The viability of AML blasts from patients and cell lines was assessed by flow cytometry after 72 hours. Arginine depletion leads to a decreased percentage of viable blasts. Representative of 2 independent experiments. (B) Expression of CAT-1, CAT-2A, and CAT-2B in blasts from 10 patients was confirmed by quantitative polymerase chain reaction (qPCR). Patients are identified by unique symbols, which are used consistently throughout the manuscript. (C) Staining of 39 bone marrow samples from AML patients at diagnosis with hematoxylin-eosin (left panel), anti-OTC (center panel), and anti-ASS (right panel). Representative marrows from 2 patients showing positive antigen staining (top) and negative antigen staining (bottom). (D) Histoscores of ASS and OTC staining in adult and pediatric AML bone marrow samples. (E) Plasma from 20 AML patients at diagnosis and 16 healthy donors were analyzed for arginine concentration by enzyme-linked immunosorbent assay (ELISA). Plasma arginine levels are significantly lower in newly diagnosed patients (P < .0001).