Journal of Isfahan Medical School

Journal of Isfahan Medical School

Dysregulation of the Wnt Signaling Pathway through Methylation of WIF1and DKK1 Genes in Patients with Acute Myeloid Leukemia (AML) at the Time of Diagnosis

Document Type : Original Article (s)

Authors
Ali Ghasemi 1
Mohsen Mohammadi 2
Abbas Ghotaslou 1
Kazem Ghaffari 3
Sadegh Abbasian 1
1 Department of Hematology, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
2 Department of Biotechnology, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
3 Instructor, Department of Hematology, School of Allied Medical Sciences, Arak University of Medical Sciences, Arak, Iran
Abstract
Background: In acute myeloid leukemia (AML), a large number of tumor suppressor genes are silenced through DNA methylation such as CDKN2B and p73. Wnt inhibitory factor 1 (WIF1) and Dickkopf-1 (DKK-1) are negative regulator of the Wnt signaling pathway. In the present study, we studied the methylation status of WIF1 and DKK-1 genes in patients with acute myeloid leukemia.Methods: Blood samples from 120 patients with acute myeloid leukemia and 25 healthy control subjects were taken. Isolated DNA was treated with sodium bisulphite and examined via methylation-specific polymerase chain reaction (MSP) with primers specific for methylated and unmethylated sequences of the WIF1 and DKK-1 genes.Findings: The frequency of aberrant hypermethylation of WIF1 and DKK-1 genes in patients with acute myeloid leukemia was determined 35.0% (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 French-American-British acute myeloid leukemia (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 myeloid leukemia. Therefore, the methylation of these genes may play a role in leukmogenesis initiation.
Keywords
DNA Methylation
WIF1
DKK
Acute myeloid leukemia
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Journal of Isfahan Medical School
Volume 32, Issue 306 - Serial Number 306
September and October 2014
Pages 1757-1766

  • Receive Date 12 August 2014
  • Accept Date 06 April 2022