NOTCH4 and acute lymphoblastic leukemia: In one study, analysis of methylation-dependent transcription regulation identified a subset of hyper-methylated and down-regulated genes in BCP-ALL, including CDKN2A, CSMD1, COL6A2, and PTPRO, whereas other genes were hypo-methylated and overexpressed including NOTCH4 and TOP1MT in relapsed children with BCP-ALL (56).