Epigenetic Silencing of WNT Inhibitory Proteins; SFRP1 and DKK3 in Acute Leukemia

Document Type : Original Article

Authors

1 Department of Clinical Pathology, Faculty of Medicine, Cairo University

2 Department of Clinical Pathology, Helwan Hospital.

3 Cairo 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

Files

Share

How to cite

Statistics