Epigenetic Silencing of WNT Inhibitory Proteins; SFRP1 and DKK3 in Acute Leukemia | ||
| Bulletin of Egyptian Society for Physiological Sciences | ||
| Article 1, Volume 32, Issue 1, June 2012, Pages 1-14 PDF (233 K) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/besps.2012.35461 | ||
| Authors | ||
| Ahmed Shams* 1; Dalia GA1; Shaimaa S2; Omar Tolba3 | ||
| 1Department of Clinical Pathology, Faculty of Medicine, Cairo University | ||
| 2Department of Clinical Pathology, Helwan Hospital. | ||
| 3Cairo University Specialized Pediatric Hospital, Pediatrics Department, Faculty of Medicine, Cairo University. | ||
| Abstract | ||
| Background: Over-activation of Wnt (derived from names of two genes; Drosophila Wingless and mouse Int-1) pathway is incriminated in leukemogenesis. Functional loss of Wnt antagonists; DKK (Dikkopf) and SFRPs (secreted frizzled-related protein), can contribute to Wnt hyper-activation. Silencing of Wnt antagonists by hypermethylation is reported in human malignancies as well as in hematopoietic malignancies. Our aim was to estimate the frequency and the possible impact of hypermethylation of the SFRP1 and DKK3 in acute leukemia. Methods: We evaluated SFRP1 and DKK3 methylation status using methylation specific polymerase chain reaction (MS-PCR) in 50 acute myeloid leukemia (AML) and 30 B-acute lymphoblastic leukemia (B-ALL) patients and 20 age and sex matched controls. Results: The frequency of methylation in B-ALL patients was 40% for SFRP1, 40% for DKK-3, in AML patients; the frequency was 44% for SFRP1, 36% for DKK-3. All the control subjects had no aberrant methylation in either SFRP1 or DKK-3. B-ALL and AML groups showed no statistical significant difference in the frequency of SFRP1 or DKK-3 methylation. B-ALL patients with M-SFRP1 had a significantly higher mean platelets count and a lower mean age compared to B-ALL patients with UM-SFRP1, no other significant clinical or hematological difference was encountered between patients with M-SFRP1 and UM-SFRP1 or between M-DKK3 and UM-DKK3 patients in the ALL or the AML group. Different B-ALL and AML prognostic cytogenetic groups showed nearby frequency of SFRP1 and DKK3 methylation. Conclusion: SFRP1 and DKK3 methylation is frequent in acute leukemia. Treatment with demethylating agents may reverse the overactivated Wnt signaling in patients with methylated phenotype. | ||
| Keywords | ||
| SFRP1; DKK3; methylation; AML; B-ALL; MS-PCR | ||
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