Fig. 5.

rs12142375 confers acute lymphoblastic leukemia risk mechanistically through modulating PDE4B gene expression. a Genomic map of the rs12142375 locus, with tracks of DNase I hypersensitive sites, H3K4me1, H3K4me2, H3K4me3, H3K27ac, H3K9ac marks, and Pol2 ChIP-seq signals in GM12878 cells. The red dots repesent the SNPs in PREs and the black d ots represent other tested SNPs in this region. rs12142375 is represented as the big red dot. b Two alleles of rs12142375 conferred different activities in our screen. Two-tailed t-test was used to calculate the p value, n = 4, **p value = 0.008. c Activities of two alleles of rs12142375 in the dual-luciferase reporter assay. The p value was calculated by two tailed t-test, n = 3, ***p value = 0.001. d PDE4B expression levels in peripheral blood mononuclear cells (normal, n = 74) and B cells of childhood acute lymphoblastic leukemia (tumor, n = 359) (data from the Haferlach Leukemia study). The p value was assessed by the Mann–Whitney U test. e Expression levels of PDE4B by qPCR in HEK293T cells expressing sgRNAs targeting the rs12142375 loci (rs12142375-sgRNA2, 24 bp upstream of the SNP, and rs12142375-sgRNA5, 11 bp downstream of the SNP) after KRAB-dCas9 activation. P values were calculated by Student’s t-test compared to the non-targeting (NT) group, n = 3, ***p value < 0.001. f eQTL results in TCGA diffuse large B-cell lymphoma dataset for the association of rs12141375 with PDE4B expression. The p value was calculated by one-tailed Student’s t-test, *p value = 0.023; ns not significant. For (b, c, e), the error bars represent standard errors