Fig. 6: Deletion of the CRE containing rs1247117 leads to increased EIF3A expression and sensitizes cells to vincristine.

a Diagram on the left showing the genomic context of the rs1247117 CRE deletion in Nalm6 cells in relation to chromatin accessibility, PU.1 binding and rs1247117. Black bar represents ATAC-seq peak, green par represents PU.1 peak, and red bar represents region deleted using CRISPR/Cas9 genome editing. b Gel shows validation of deletion using primers flanking deleted region. Arrow points to PCR fragment with deletion in heterogeneous Nalm6 cell pools harboring deletion compared to wild-type parental Nalm6 cells. c EIF3A gene expression is upregulated upon deletion of the CRE containing rs1247117. RT-qPCR data show the mean ± SD of three independent experiments. Two-tailed Student’s T test. d Western blots and quantification showing increased EIF3A expression in rs1247117 del Nalm6 cells. Blots shown are representative of four independent experiments. Quantification data show the mean ± SD. Two-tailed Student’s T tests, n = 4. e–g Drug sensitivity data comparing viability relative to vehicle treatment of wild-type parental Nalm6 cells and Nalm6 cells with rs1247117 CRE deletion after vincristine (VCR) treatment for 24 (n = 3), 48 (n = 3) and 72 (n = 3) hours at the indicated concentrations. Non-linear regression and F test analysis indicate that these dose-response curves are significantly different. h Caspase 3/7 activity assays comparing Caspase activity relative to vehicle treatment of wild-type parental Nalm6 cells and Nalm6 cells with rs1247117 CRE deletion after vincristine (VCR) treatment for 72 hours at the indicated concentrations (n = 3). Dose-response curves of non-linear regression indicate that these curves are significantly different. Non-linear regression and F test analysis indicate that these dose-response curves are significantly different. All source data are provided in the Source Data file.