ArticleCancer science2010
Epigenetic regulation of the non-canonical Wnt pathway in acute myeloid leukemia.
Article in Cancer science, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 48 citations in OpenAlex.
- NUC-7738 regulates β-catenin signalling resulting in reduced proliferation and self-renewal of AML cells.PloS one · 2022Trial
- Wnt/CaOncology letters · 2025Review
- Review
- The antitumor effects of WNT5A against hematological malignancies.Journal of cell communication and signaling · 2023Article
- "Losing the Brakes"-Suppressed Inhibitors Triggering UncontrolledCurrent issues in molecular biology · 2023Article
- Memory B-cell like chronic lymphocytic leukaemia is associated with specific methylation profile ofEpigenetics · 2022Article
- WNT5B in Physiology and Disease.Frontiers in cell and developmental biology · 2021Review
- Deciphering the role of Wnt signaling in acute myeloid leukemia prognosis: how alterations in DNA methylation come into play in patients' prognosis.Journal of cancer research and clinical oncology · 2020Review
- Loss of Histone Locus Bodies in the Mature Hemocytes of Larval Lymph Gland Result in Hyperplasia of the Tissue inInternational journal of molecular sciences · 2020Article
- Wnt Signalling in Acute Myeloid Leukaemia.Cells · 2019Review
- Aberrant Wnt Signaling Pathway in the Hematopoietic Stem/Progenitor Compartment in Experimental Leukemic Animal.Journal of cell communication and signaling · 2019Article
- Signaling Pathways in Leukemic Stem Cells.Advances in experimental medicine and biology · 2019Review
- mRNA expression of nuclear factor of activated T-cells, cytoplasmic 2 (NFATc2) and peroxisome proliferator-activated receptor gamma (PPARG) transcription factors in colorectal carcinoma.Bosnian journal of basic medical sciences · 2017Article
- Mesenchymal Stem Cells in Myeloid Malignancies: A Focus on Immune Escaping and Therapeutic Implications.Stem cells international · 2017Review
- Aberrant Wnt Signaling in Leukemia.Cancers · 2016Review
- Mesenchymal Stem and Progenitor Cells in Normal and Dysplastic Hematopoiesis-Masters of Survival and Clonality?International journal of molecular sciences · 2016Review
- A Possible Role for WNT5A Hypermethylation in Pediatric Acute Lymphoblastic Leukemia.Turkish journal of haematology : official journal of Turkish Society of Haematology · 2015Article
- An integrated approach of gene expression and DNA-methylation profiles of WNT signaling genes uncovers novel prognostic markers in acute myeloid leukemia.BMC bioinformatics · 2015Article
- Frizzled-8 receptor is activated by the Wnt-2 ligand in non-small cell lung cancer.BMC cancer · 2013Article
- Article
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Wnt5a is a member of the Wnt family of proteins that signals through the non-canonical Wnt/Ca(2+)pathway to suppress cyclin D1. Deregulation of this pathway has been found in animal models suggesting that it acts as tumour suppressor in acute myeloid leukemia (AML). Although DNA methylation is the main mechanism of regulation of the canonical Wnt pathway in AML, the role of WNT5A abnormalities has never been evaluated in this clinical setting. The methylation status of WNT5A promoter-exon 1 was analyzed by methylation-specific PCR and sequencing in eleven AML-derived cell lines and 252 AML patients. We observed WNT5A hypermethylation in seven cell lines and in 43% (107/252) of AML patients. WNT5A methylation was associated with decreased WNT5A expression (P < 0.001) that was restored after exposure to 5-Aza-2'-deoxycytidine. Moreover, WNT5A hypermethylation correlated with upregulation of CYCLIN D1 expression (P < 0.001). Relapse (15%vs 37%, P < 0.001) and mortality (61%vs 79%, P = 0.004) rates were lower for patients in the non-methylated group. Disease-free survival and overall survival at 6 and 7 years, respectively, were 60% and 27% for unmethylated patients and 20% and 0% for hypermethylated patients (P = 0.0001 and P = 0.04, respectively). Interestingly, significant differences were also observed when the analysis was carried out according to cytogenetic risk groups. We demonstrate that WNT5A, a putative tumor suppressor gene in AML, is silenced by methylation in this disease and that this epigenetic event is associated with upregulation of CYCLIN D1 expression and confers poor prognosis in patients with AML.
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