NR2E3 and acute lymphoblastic leukemia: To determine whether impaired dCK activity underlies innate resistance to PNPi and dG in non-T-ALL lines, we employed an liquid chromatography–tandem mass spectrometry–multiple reaction monitoring (LC-MS/MS-MRM) approach developed by our group (18) to simultaneously evaluate the contributions of dCK-dependent salvage and ribonucleotide reductase–dependent (RNR-dependent) de novo biosynthesis to DNA replication using [15N3]-labeled deoxycytidine ([15N3]dC) and [13C6]glucose, respectively (Supplemental Figure 1E).