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

Background: 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 Methods: 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. Results: 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. Conclusion: 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.