ArticleLeukemia2018
Hedgehog pathway mutations drive oncogenic transformation in high-risk T-cell acute lymphoblastic leukemia.
Article in Leukemia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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
41 citing papers in PubMed, 55 citations in OpenAlex.
- Review
- Curcumin and Methotrexate: A Promising Combination for Osteosarcoma Treatment via Hedgehog Pathway Inhibition.International journal of molecular sciences · 2024Article
- A simple and scalable zebrafish model of Sonic hedgehog medulloblastoma.Cell reports · 2024Article
- Zebrafish-A Suitable Model for Rapid Translation of Effective Therapies for Pediatric Cancers.Cancers · 2024Review
- Association of CDKN2A/B mutations, PD-1, and PD-L1 with the risk of acute lymphoblastic leukemia in children.Journal of cancer research and clinical oncology · 2023Article
- Review
- Review
- Understanding the Roles of the Hedgehog Signaling Pathway during T-Cell Lymphopoiesis and in T-Cell Acute Lymphoblastic Leukemia (T-ALL).International journal of molecular sciences · 2023Review
- The role of Hedgehog and Notch signaling pathway in cancer.Molecular biomedicine · 2022Review
- Specific lncRNA signatures discriminate childhood acute leukaemias: a pilot study.Cancer cell international · 2022Article
- Pluripotent Stem Cells: Cancer Study, Therapy, and Vaccination.Stem cell reviews and reports · 2021Review
- A Synopsis of Signaling Crosstalk of Pericytes and Endothelial Cells in Salivary Gland.Dentistry journal · 2021Review
- The Role of Smoothened-Dependent and -Independent Hedgehog Signaling Pathway in Tumorigenesis.Biomedicines · 2021Review
- Responsiveness to Hedgehog Pathway Inhibitors in T-Cell Acute Lymphoblastic Leukemia Cells Is Highly Dependent on 5'AMP-Activated Kinase Inactivation.International journal of molecular sciences · 2021Article
- Comprehending the crosstalk between Notch, Wnt and Hedgehog signaling pathways in oral squamous cell carcinoma - clinical implications.Cellular oncology (Dordrecht, Netherlands) · 2021Review
- Medulloblastoma drugs in development: Current leads, trials and drawbacks.European journal of medicinal chemistry · 2021Review
- Cross-talk between GLI transcription factors and FOXC1 promotes T-cell acute lymphoblastic leukemia dissemination.Leukemia · 2021Article
- PRL3 enhances T-cell acute lymphoblastic leukemia growth through suppressing T-cell signaling pathways and apoptosis.Leukemia · 2021Article
- Article
- High Circulating Sonic Hedgehog Protein Is Associated With Poor Outcome in EGFR-Mutated Advanced NSCLC Treated With Tyrosine Kinase Inhibitors.Frontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
19 authors at 8 institutions in 1 country.
Funding
Abstract
The role of Hedgehog signaling in normal and malignant T-cell development is controversial. Recently, Hedgehog pathway mutations have been described in T-ALL, but whether mutational activation of Hedgehog signaling drives T-cell transformation is unknown, hindering the rationale for therapeutic intervention. Here, we show that Hedgehog pathway mutations predict chemotherapy resistance in human T-ALL, and drive oncogenic transformation in a zebrafish model of the disease. We found Hedgehog pathway mutations in 16% of 109 childhood T-ALL cases, most commonly affecting its negative regulator PTCH1. Hedgehog mutations were associated with resistance to induction chemotherapy (P = 0.009). Transduction of wild-type PTCH1 into PTCH1-mutant T-ALL cells induced apoptosis (P = 0.005), a phenotype that was reversed by downstream Hedgehog pathway activation (P = 0.007). Transduction of most mutant PTCH1, SUFU, and GLI alleles into mammalian cells induced aberrant regulation of Hedgehog signaling, indicating that these mutations are pathogenic. Using a CRISPR/Cas9 system for lineage-restricted gene disruption in transgenic zebrafish, we found that ptch1 mutations accelerated the onset of notch1-induced T-ALL (P = 0.0001), and pharmacologic Hedgehog pathway inhibition had therapeutic activity. Thus, Hedgehog-activating mutations are driver oncogenic alterations in high-risk T-ALL, providing a molecular rationale for targeted therapy in this disease.
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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.