TET2 Promoter DNA Methylation and Expression in Childhood Acute Lymphoblastic Leukemia


Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran


The ten-eleven-translocation-2 (TET2) gene is a novel tumor suppressor gene involved in several hematological malignancies of myeloid and lymphoid origin. Besides loss-of-function mutations and deletions, hypermethylation of the CpG island at the TET2 promoter has been found in human cancers. The TET2 encoded protein regulates DNA methylation. The present study aimed to examine DNA promoter methylation of TET2 in 100 childhood acute lymphoblastic leukemia (ALL) cases and 120 healthy children in southeast Iran. In addition, mRNA expression levels were assessed in 30 new cases of ALL and 32 controls. Our ndings indicated that promoter methylation of TET2 signi cantly increases the risk of ALL (OR2.60, 95% CI1.31-5.12, p0.0060) in comparison with absent methylation. Furthermore, the TET2 gene was signi cantly downregulated in childhood ALL compared to healthy children (p0.0235). The results revealed that hypermethylation and downregulation of TET2 gene may play a role in predisposition to childhood ALL. Further studies with larger sample sizes and different ethnicities are needed to con rm our ndings.