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.