DNA methylation is a dynamic process influencing gene expression by altering either coding or non-coding loci. Despite advances in treatment of Acute Lymphoblastic Leukemia (ALL); relapse occurs in approximately 20% of patients. Nowadays, epigenetic factors are considered as one of the most effective mechanisms in pathogenesis of malignancies. These factors are reversible elements which can be potentially regarded as therapy targets and disease prognosis. DNA methylation, which primarily serves as transcriptional suppressor, mostly occurs in CpG islands of the gene promoter regions. This was shown as a key epigenetic factor in inactivating various tumor suppressor genes during cancer initiation and progression.

We aimed to review methylation status of key genes involved in hematopoietic malignancies such as IKZF1, CDKN2B, TET2, CYP1B1, SALL4, DLC1, DLX family, TP73, PTPN6, and CDKN1C; and their significance in pathogenesis of ALL. The DNA methylation alterations in promoter regions of the genes have been shown to play crucial roles in tumorigenesis. Methylation -based inactivation of these genes has also been reported as associated with prognosis in acute leukemia. In this review, we also addressed the association of gene expression and methylation pattern in ALL patients.