Dysregulation of the WNT Signaling Pathway Through Methylation of Wnt Inhibitory Factor 1 and Dickkopf-1 Genes among AML Patients at the Time of Diagnosis

In acute myeloblastic leukemia, a large number of tumor suppressor genes are silenced through DNA methylation such as CDKN2B & p73. Wnt inhibitory factor 1 (WIF1) and Dickkopf-3 (DKK-1) are negative regulators of Wnt signaling pathway. In the present study, we evaluated the methylation status of WIF1 and DKK-1 genes in acute myeloblastic leukemia patients. Patients and Blood samples were taken from 120 AML patients and 25 healthy control subjects. DNA was isolated, treated with sodium bisulphite, and examined using methylation-specific polymerase chain reaction (MSP) with primers specific for methylated and unmethylated sequences of the WIF1 and DKK-1 genes. The frequency of aberrant hypermethylation of WIF1 and DKK-1 genes in acute myeloblastic leukemia patients were determined to be 35% (42/120) and 28.3% (34/120), respectively. In addition, for all subjects in control group, methylation of WIF1 and DKK-1 genes were negative. Patients with M0 subtype of FAB-AML had the highest incidence of hypermethylation of WIF1 (P = 0.003) and DKK-1 (P = 0.005) genes. The present study showed that, like many solid tumors, WIF1 and DKK-1 genes methylation also occurs in acute myeloblastic leukemia. The study of other antagonists of Wnt signaling pathways are recommended. Key words: AML, Wnt inhibitory factor 1, dickkopf, DNA methylation.