PTC299 inhibits the proliferation of MDS cell lines. (A) Schematic representation of the pyrimidine synthesis pathway. CAD, carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase; CDA, cytidine deaminase; UMPS, UMP synthase. (B) Growth of HL-60 and THP-1 AML cells treated with the indicated concentrations of PTC299. The numbers of viable cells are shown as means ± SD (n = 3). ****P < .001 by a 1-way ANOVA. (C) Flow cytometric histograms showing CD11b expression levels on HL-60 and THP-1 cells treated with the indicated concentrations of PTC299 for 7 days. (D) Growth of MDS-L and SKM-1 MDS cells treated with the indicated concentrations of PTC299. The numbers of viable cells are shown as means ± SD (n = 3). *P < .05, ***P < .001 by 1-way ANOVA. (E) Mean fluorescent intensity (MFI) of CD38 on MDS-L and SKM-1 cells treated with the indicated concentrations of PTC299 for 7 days. Data are shown as means ± SD (n = 3). *P < .05, **P < .01, ***P < .001 by 1-way ANOVA. (F) MDS-L and SKM-1 cells were treated with PTC299 in the presence of an excess of uridine (100 μM) for 7 days. The numbers of viable cells are shown as means ± SD (n = 3). *P < .05, **P < .01, ***P < .001; ns, not significant by 1-way ANOVA. (G) MTS assays showing the viability of MDS-L and SKM-1 cells treated with the indicated doses of PTC299 with or without 100 μM uridine on day 7 of culture. Data represent mean ± SD (n = 4). **P < .01 by the Student t test.