Hypermethylation of Wnt antagonist gene promoters and activation of Wnt pathway in myelodysplastic marrow cells.

Autor: Masala E; UF Ematologia, Azienda Ospedaliero Universitaria Careggi, University of Florence, Florence, Italy., Valencia A, Buchi F, Nosi D, Spinelli E, Gozzini A, Sassolini F, Sanna A, Zecchi S, Bosi A, Santini V
Jazyk: angličtina
Zdroj: Leukemia research [Leuk Res] 2012 Oct; Vol. 36 (10), pp. 1290-5. Date of Electronic Publication: 2012 Jun 27.
DOI: 10.1016/j.leukres.2012.05.023
Abstrakt: We observed aberrant gene methylation of Wnt antagonists: sFRP1, sFRP2, sFRP4, sFRP5 and DKK1 in marrow cells of 55 MDS cases. Methylation of Wnt antagonist genes was associated with activation of the Wnt signaling pathway, consistent with the up-regulation of the Wnt downstream genes TCF1 and LEF1. Azacitidine exposure induced demethylation of Wnt-antagonist gene promoters and reduction of the non-phosphorylated β-catenin (NPBC) which is prevalent during Wnt pathway inactivation. Presence of ≥5% of bone marrow blasts was associated with methylation of sFRP1 and DKK1 and with methylation of more than two of the five Wnt antagonist genes.
(Copyright © 2012 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE