LAUSR

F IGURE 1 Combined ENT1 and DCK gene expression levels are highly associated with ara-G sensitivity in humanT-ALL cell lines. A, The schema of pharmacological activation pathway of nelarabine. B, Ara-G sensitivity of humanT-ALL cell lines was determined using alamarBlue cell viability assay after a 72-h incubation with seven concentrations of ara-G. The representative doseresponse curves are shown. The vertical axis indicates % viability and the horizontal axis indicates ara-G concentrations (μM). The IC50 value of each cell line is indicated on the right. C, Twodimensional analysis of ENT1 and DCK gene expression levels in humanT-ALL cell lines. Filled and open circles represent ara-Gsensitive (IC50 < 10 μM) and araG-resistant (IC50 ≥ 10 μM) T-ALL cell lines, respectively. The correlation coefficient and P value are shown. D, Sum of ENT1 and DCK relative gene expression levels in ara-G-sensitive and araG-resistant T-ALL cell lines. P value in Mann-Whitney analysis is shown. E, Intracellular ara-GTP levels inT-ALL cell lines treated with ara-G. Intracellular ara-GTP levels (per 1 mg of total cellular protein) measured by highperformance liquid chromatography in three ara-Gsensitive and three ara-Gresistant cell lines incubated with 10 μM of ara-G for 5 h are indicated. P value in MannWhitney analysis is shown Received: 7 June 2019 Revised: 15 July 2019 Accepted: 16 July 2019