ArticleCancers2020
Small Molecule Inhibitors of Microenvironmental Wnt/β-Catenin Signaling Enhance the Chemosensitivity of Acute Myeloid Leukemia.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed.
- The Role of the Bone Marrow Microenvironment in the Pathogenesis of Acute Myeloid Leukemia.Biomedicines · 2026Review
- Role of the Wnt5A pathway in resistance to immune checkpoint inhibitors in advanced Non-Small Cell Lung Cancer.Cancer immunology, immunotherapy : CII · 2026Article
- Targeting the WNT/β-Catenin Pathway in Hematological Malignancies: From Molecular Pathogenesis to Emerging Therapeutic Strategies.Biomolecules · 2026Review
- The interplay between non-coding RNAs and Wnt signaling pathway in leukemia: A narrative review.BioImpacts : BI · 2026Review
- Thy-1 knockdown promotes the osteogenic differentiation of GMSCs via the Wnt/β-catenin pathway.Journal of cellular and molecular medicine · 2023Article
- "Losing the Brakes"-Suppressed Inhibitors Triggering UncontrolledCurrent issues in molecular biology · 2023Article
- Bone Marrow Microenvironment as a Source of New Drug Targets for the Treatment of Acute Myeloid Leukaemia.International journal of molecular sciences · 2022Review
- Canonical Wnt signaling enhances pro-inflammatory response to titanium by macrophages.Biomaterials · 2022Article
- The Therapeutic Role of PNU-74654 in Hepatocellular Carcinoma May Involve Suppression of NF-κB Signaling.Medicina (Kaunas, Lithuania) · 2022Article
- PNU-74654 Suppresses TNFR1/IKB Alpha/p65 Signaling and Induces Cell Death in Testicular Cancer.Current issues in molecular biology · 2022Article
- GSK-3: a multifaceted player in acute leukemias.Leukemia · 2021Review
- Targeting Casein Kinase 1 (CK1) in Hematological Cancers.International journal of molecular sciences · 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
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Wnt/β-catenin signaling has been reported in Acute Myeloid leukemia, but little is known about its significance as a prognostic biomarker and drug target. In this study, we first evaluated the correlation between expression levels of Wnt molecules and clinical outcome. Then, we studied-in vitro and in vivo-the anti-leukemic value of combinatorial treatment between Wnt inhibitors and classic anti-leukemia drugs. Higher levels of β-catenin, Ser675-phospho-β-catenin and GSK-3α (total and Ser 9) were found in AML cells from intermediate or poor risk patients; nevertheless, patients presenting high activity of Wnt/β-catenin displayed shorter progression-free survival (PFS) according to univariate analysis. In vitro, many pharmacological inhibitors of Wnt signalling, i.e., LRP6 (Niclosamide), GSK-3 (LiCl, AR-A014418), and TCF/LEF (PNU-74654) but not Porcupine (IWP-2), significantly reduced proliferation and improved the drug sensitivity of AML cells cultured alone or in the presence of bone marrow stromal cells. In vivo, PNU-74654, Niclosamide and LiCl administration significantly reduced the bone marrow leukemic burden acting synergistically with Ara-C, thus improving mouse survival. Overall, our study demonstrates the antileukemic role of Wnt/β-catenin inhibition that may represent a potential new therapeutics strategy in AML.
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Registered trials
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