ArticleLeukemia & lymphoma2010
Acute myeloid leukemia is characterized by Wnt pathway inhibitor promoter hypermethylation.
Article in Leukemia & lymphoma, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 78 citations in OpenAlex.
- Review
- Review
- Review
- Transcriptomic Context ofBiomedicines · 2023Article
- Understanding the Wnt Signaling Pathway in Acute Myeloid Leukemia Stem Cells: A Feasible Key against Relapses.Biology · 2023Review
- "Losing the Brakes"-Suppressed Inhibitors Triggering UncontrolledCurrent issues in molecular biology · 2023Article
- Targeting β-catenin in acute myeloid leukaemia: past, present, and future perspectives.Bioscience reports · 2022Review
- Characteristics of leukemic stem cells in acute leukemia and potential targeted therapies for their specific eradication.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Concurrent Evaluation of the Expression and Methylation ofIranian journal of medical sciences · 2021Article
- Bimodal expression ofEJHaem · 2021Article
- Gene Methylation and Silencing of WIF1 Is a Frequent Genetic Abnormality in Mantle Cell Lymphoma.International journal of molecular sciences · 2021Article
- Sry-related High Mobility Group Box 17 Functions as a Tumor Suppressor by Antagonizing the Wingless-related Integration Site Pathway.Journal of cancer prevention · 2020Review
- 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
- Overcoming Wnt-β-catenin dependent anticancer therapy resistance in leukaemia stem cells.Nature cell biology · 2020Article
- Targeting signalling pathways and the immune microenvironment of cancer stem cells - a clinical update.Nature reviews. Clinical oncology · 2020Review
- The Role of Notch and Wnt Signaling in MSC Communication in Normal and Leukemic Bone Marrow Niche.Frontiers in cell and developmental biology · 2020Review
- WNT Signaling in Hematological Malignancies.Frontiers in oncology · 2020Review
- WNT Signaling in Tumors: The Way to Evade Drugs and Immunity.Frontiers in immunology · 2019Review
- Consecutive epigenetically-active agent combinations act inOncotarget · 2018Article
- Suppression of miR-708 inhibits the Wnt/β-catenin signaling pathway by activating DKK3 in adult B-all.Oncotarget · 2017Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Nuclear localization of non-phosphorylated, active beta-catenin is a measure of Wnt pathway activation and is associated with adverse outcome in patients with acute myeloid leukemia (AML). While genetic alterations of the Wnt pathway are infrequent in AML, inhibitors of this pathway are silenced by promoter methylation in other malignanices. Leukemia cell lines were examined for Wnt pathway inhibitor methylation and total beta-catenin levels, and had frequent methylation of Wnt inhibitors and upregulated beta-catenin by Western blot and immunofluorescence. One hundred sixty-nine AML samples were examined for methylation of Wnt inhibitor genes. Diagnostic samples from 72 patients with normal cytogenetics who received standard high-dose induction chemotherapy were evaluated for associations between methylation and event-free or overall survival. Extensive methylation of Wnt pathway inhibitor genes was observed in cell lines, and 89% of primary AML samples had at least one methylated gene: DKK1 (16%), DKK3 (8%), RUNX3 (27%), sFRP1 (34%), sFRP2 (66%), sFRP4 (9%), sFRP5 (54%), SOX17 (29%), and WIF1 (32%). In contrast to epithelial tumors, methylation of APC (2%) and RASSF1A (0%) was rare. In patients with AML with normal cytogenetics, sFRP2 and sFRP5 methylation at the time of diagnosis was associated with an increased risk of relapse, and sFRP2 methylation was associated with an increased risk for death. In patients with AML: (a) there is a high frequency of Wnt pathway inhibitor methylation; (b) Wnt pathway inhibitor methylation is distinct from that observed in epithelial malignancies; and (c) methylation of sFRP2 and sFRP5 may predict adverse clinical outcome in patients with normal karyotype AML.
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