A G, A G, M M, K G, S A. 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. Iranian Journal of Blood and Cancer 2014; 7 (1) :11-17
URL:
http://ijbc.ir/article-1-517-en.html
Abstract: (7238 Views)
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.
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Original Article |
Subject:
Pediatric Hematology & Oncology Received: 2014/12/11 | Accepted: 2014/12/11 | Published: 2014/12/11