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. 2021 Dec 14;12:7190. doi: 10.1038/s41467-021-27329-x

Fig. 6. Differential expression of SLC16A1 and SLC16A3 determines sensitivity to AZD3965.

Fig. 6

a Average dose–response data of AZD3965 expressed as percentage survival (n = 15 biologically independent cell lines in technical duplicate of each concentration). The sensitivity of AZD3965 in the two sensitive CML cell lines, K-562 and BV-173, is highlighted in red. Error bars indicate mean ± SD. b Level of gene expression of SLC16A1 and SLC16A3 in publicly available datasets from the Dependency Map Portal29,80. c Immunoblot analysis of SLC16A1 and SLC16A3 expression in K-562 cells lentivirally transduced with empty vector, SLC16A1 or SLC16A3-cDNA. Data are representative of two independent experiments. d Average response to AZD3965 in K-562 wild type, empty vector, and SLC16A1 or SLC16A3 overexpressing cells. Error bars indicate standard deviation of the mean of technical triplicates. Data are representative of two independent experiments. e Expression of SLC16A1 and SLC16A3 in MV4-11 AML cells transduced with the indicated sgRNAs. Data are representative of two independent experiments. f Average response to AZD3965 in MV4-11 wild type, sgRen control infected cells, and SLC16A1 or SLC16A3 deficient cells. Error bars indicate standard deviation of the mean of technical triplicates. Data are representative of two independent experiments. g Volcano plot showing differences in gene expression between AZD3965 sensitive (K-562 and BV-173) and nonsensitive lines (the remaining 12 for which gene expression data were available). Each point represents one gene. An unpaired two-sample, two-sided t-test was performed for each gene. The y-axis corresponds to FDR adjusted P values (using Benjamini–Hochberg correction). The horizontal red dotted line signifies the 5% FDR cutoff. h A correlation plot of SLC16A1 and SLC16A3 expression in the 205 hematological cancer cell lines covered by the Dependency Map from the Broad Institute (expression data 20Q2)40. The diagonal dotted line indicates an SLC16A1/SLC16A3 expression ratio of 3 or higher highlighting cell lines predicted to be sensitive to AZD3965 (n = 44) that are annotated per lineage and disease subtype. BV-173 and K-562 are labeled for reference. The names of the remaining cell lines and the corresponding SLC16A1/SLC16A3 expression ratio are shown in Supplementary Fig. 9g.