AKR1C3 expression in primary ALL and PDX cells and quantification of DNA ICLs. (a-b) RNA-Seq data of primary (a) and PDX (b) B-ALL versus T-ALL cells expressed as FPKM on a log2 scale. (c-d) AKR1C3 mRNA (c) and protein (d) expression levels in a panel of 6 B-ALL, 6 T-ALL and 6 ETP-ALL PDXs. A representative immunoblot is shown in (d). (e-f) Correlations of PDX cell survival following treatment with OBI-3424 and AKR1C3 protein expression at 100 nM (e) or 10 nM (f) OBI-3424. (g) Comet assay results showing DNA ICL Indices in 3 ALL PDXs (ALL-8, ETP-2, ALL-19) following OBI-3424 treatment (4 h). (h) Representative comet images from G are shown for ALL-8. In (a) and (b) bars represent the median and interquartile range. Data in c, d and g are displayed as the mean ± SEM of biological triplicates. Solid and dashed lines in e and f represent linear regression and 95% confidence interval, respectively.