Aberrant methylation of imprinted gene cluster at 7q21 in BCP-ALL. (A) Methylation of CpG islands in the PEG10, DLX5, and ASNS genes in sperm and maternally derived MCT. The position of CG dinucleotides is indicated in the top panel. (B) Methylation of PEG10, DLX5, and ASNS in normal hematopoietic cells and 3 BCP-ALL cell lines that have highly (KOPN57bi), intermediately (KOCL50), and weakly (Nalm6) methylated ASNS. The top panel is a schematic representation of gene configuration at 7q21. P indicates paternally expressed genes and M indicates maternally expressed genes. Histograms indicate the mean percent methylation of each gene. (C) An evolutionary tree of mammals with the alignment of genes located at 7q21-22 in humans. Numbers indicate the chromosome. (D) Methylation of the imprinted gene cluster at 7q21 in BCP-ALL cases of NOPHO, CCCS, and TCCSG cohorts. In the top panel, heat maps indicate methylation status in BCP-ALL and bone marrow (BM) samples at complete remission in the NOPHO cohort. In the bottom panel, heat maps indicate the coefficient of correlation between the percent methylation of each gene and that of ASNS. Asterisks indicate significant correlation (R² > 0.2). (E) Correlation between ASNS methylation and methylation of representative genes in BCP-ALL cases of 3 cohorts. Vertical and horizontal axes indicate the mean percent methylation of ASNS and that of each gene, respectively. The coefficient of correlation is indicated in each panel.