title: Hypermethylation of Wnt antagonist gene promoters and activation of Wnt pathway in myelodysplastic marrow cells.
abstract: 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.
authors: UF Ematologia, Azienda Ospedaliero Universitaria Careggi, University of Florence, Florence, Italy.
authors: Erico
authors: E
authors: Masala
authors: Ana
authors: A
authors: Valencia
authors: Francesca
authors: F
authors: Buchi
authors: Daniele
authors: D
authors: Nosi
authors: Elena
authors: E
authors: Spinelli
authors: Antonella
authors: A
authors: Gozzini
authors: Francesca
authors: F
authors: Sassolini
authors: Alessandro
authors: A
authors: Sanna
authors: Sandra
authors: S
authors: Zecchi
authors: Alberto
authors: A
authors: Bosi
authors: Valeria
authors: V
authors: Santini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D064007:Ataxia Telangiectasia Mutated Proteins; D001374:Azacitidine / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D019175:DNA Methylation; D005260:Female; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D000964:Antimetabolites, Antineoplastic; D064007:Ataxia Telangiectasia Mutated Proteins; D001374:Azacitidine; D018797:Cell Cycle Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; D036341:Intercellular Signaling Peptides and Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051153:Wnt Proteins; C501126:DKK1 protein, human; C496487:HNF1A protein, human; C497573:LEF1 protein, human; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins; C118723:SFRP4 protein, human; C576597:ATR protein, human