ArticleBritish journal of haematology2014
Wnt inhibition leads to improved chemosensitivity in paediatric acute lymphoblastic leukaemia.
Article in British journal of haematology, 2014. 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, 82 citations in OpenAlex.
- MAPK signaling cascades mediate distinct glucocorticoid resistance mechanisms in pediatric leukemia.Blood · 2015Trial
- Loss of TBL1XR1 disrupts glucocorticoid receptor recruitment to chromatin and results in glucocorticoid resistance in a B-lymphoblastic leukemia model.The Journal of biological chemistry · 2014Trial
- Chemotherapy-driven expression of WNT ligands in bone marrow stromal cells contributes to chemoresistance in acute lymphoblastic leukaemia.British journal of haematology · 2026Article
- Hepatocellular carcinoma-linkediScience · 2026Article
- Targeting Wnt Signaling in Acute Lymphoblastic Leukemia.Cancers · 2025Review
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- CMYC-initiated HNF1A-AS1 overexpression maintains the stemness of gastric cancer cells.Cell death & disease · 2024Article
- Mutual antagonism between glucocorticoid and canonical Wnt signaling pathways in B-cell acute lymphoblastic leukemia.Blood advances · 2023Article
- Targeting N-cadherin (CDH2) and the malignant bone marrow microenvironment in acute leukaemia.Expert reviews in molecular medicine · 2023Review
- β-catenin-IRP2-primed iron availability to mitochondrial metabolism is druggable for active β-catenin-mediated cancer.Journal of translational medicine · 2023Article
- Modulating β-catenin/BCL9 interaction with cell-membrane-camouflaged carnosic acid to inhibit Wnt pathway and enhance tumor immune response.Frontiers in immunology · 2023Article
- Targeting β-catenin in acute myeloid leukaemia: past, present, and future perspectives.Bioscience reports · 2022Review
- The Bone Marrow Niche in B-Cell Acute Lymphoblastic Leukemia: The Role of Microenvironment from Pre-Leukemia to Overt Leukemia.International journal of molecular sciences · 2021Review
- Article
- Inhibition of Wnt-β-Catenin Signaling by ICRT14 Drug Depends of Post-Transcriptional Regulation by HOTAIR in Human Cervical Cancer HeLa Cells.Frontiers in oncology · 2021Article
- Targeting the Wnt/β-catenin signaling pathway in cancer.Journal of hematology & oncology · 2020Review
- Evolution of the Epigenetic Landscape in Childhood B Acute Lymphoblastic Leukemia and Its Role in Drug Resistance.Cancer research · 2020Article
- B-ALL Complexity: Is Targeted Therapy Still A Valuable Approach for Pediatric Patients?Cancers · 2020Review
- Wnt Signaling in Leukemia and Its Bone Marrow Microenvironment.International journal of molecular sciences · 2020Review
- ESRRB regulates glucocorticoid gene expression in mice and patients with acute lymphoblastic leukemia.Blood advances · 2020Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
While childhood acute lymphoblastic leukaemia (ALL) is now highly curable, the dismal prognosis for children who relapse warrants novel therapeutic approaches. Previously, using an integrated genomic analysis of matched diagnosis-relapse paired samples, we identified overactivation of the Wnt pathway as a possible mechanism of recurrence. To validate these findings and document whether Wnt inhibition may sensitize cells to chemotherapy, we analysed the expression of activated β-catenin (and its downstream target BIRC5) using multiparameter phosphoflow cytometry and tested the efficacy of a recently developed Wnt inhibitor, iCRT14, in ALL cell lines and patient samples. We observed increased activation of β-catenin at relapse in 6/10 patients. Furthermore, treatment of leukaemic cell lines with iCRT14 led to significant downregulation of Wnt target genes and combination with traditional chemotherapeutic drugs resulted in a synergistic decrease in viability as well as a significant increase in apoptotic cell death. Finally, pre-treatment of purified blasts from patients with relapsed leukaemia with the Wnt inhibitor followed by exposure to prednisolone, restored chemosensitivity in these cells. Our results demonstrate that overactivation of the Wnt pathway may contribute to chemoresistance in relapsed childhood ALL and that Wnt-inhibition may be a promising therapeutic approach.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.