ArticleHaematologica2021
Whole Exome Sequencing reveals NOTCH1 mutations in anaplastic large cell lymphoma and points to Notch both as a key pathway and a potential therapeutic target.
Article in Haematologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.
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Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 57 citations in OpenAlex.
- Pooled it
- A genetic profiling guideline to support diagnosis and clinical management of lymphomas.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Guideline
- From molecular pathogenesis to novel Therapeutic approaches - a review of recent advances in the treatment of peripheral T cell Lymphomas.Biomarker research · 2026Review
- Targeting the Notch1-YY1-ICAM1 Signaling Axis Enhances the Efficacy of Immunotherapy in HCC by Activating CD8Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Does CD30 loss preclude the diagnosis of anaplastic lymphoma kinase-positive anaplastic large cell lymphoma? Insights from a rare case.CytoJournal · 2026Article
- Establishment and characterization of a novel patient-derived TP63-rearranged anaplastic large-cell lymphoma model PTCL-S1.Human cell · 2025Article
- ProteinMolecules (Basel, Switzerland) · 2025Review
- Circulating tumor DNA in lymphoma: technologies and applications.Journal of hematology & oncology · 2025Review
- Notch pathway inhibition with crenigacestat (LY3039478) in a phase I first-in-human clinical trial for patients with relapsed or refractory non-Hodgkin lymphoma and B-cell chronic lymphocytic leukemia.Therapeutic advances in drug safety · 2025Article
- Comprehensive genomic analysis reveals molecular heterogeneity in pediatric ALK-positive anaplastic large cell lymphoma.Leukemia · 2025Article
- Recurrent somatic mutations of FAT family cadherins induce an aggressive phenotype and poor prognosis in anaplastic large cell lymphoma.British journal of cancer · 2024Article
- Glycosylation: mechanisms, biological functions and clinical implications.Signal transduction and targeted therapy · 2024Review
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- Liquid biopsy in T-cell lymphoma: biomarker detection techniques and clinical application.Molecular cancer · 2024Review
- Diagnostic and prognostic molecular pathology of lymphoid malignancies.Virchows Archiv : an international journal of pathology · 2024Review
- Primary Cutaneous CD30-Positive Lymphoproliferative Disorders-Current Therapeutic Approaches with a Focus on Brentuximab Vedotin.Journal of clinical medicine · 2024Review
- Pathobiology of nodal peripheral T-cell lymphomas: current understanding and future directions.Haematologica · 2023Review
- Patient-derived xenograft models of ALK+ ALCL reveal preclinical promise for therapy with brigatinib.British journal of haematology · 2023Article
- SOHO State of the Art Updates and Next Questions | New Pathways and New Targets in PTCL: Staying on Target.Clinical lymphoma, myeloma & leukemia · 2023Review
- Article
Corrections and comments
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Authors and funding
34 authors at 18 institutions in 11 countries.
Funding
Abstract
Patients diagnosed with Anaplastic Large Cell Lymphoma (ALCL) are still treated with toxic multi-agent chemotherapy and as many as 25-50% of patients relapse. To understand disease pathology and to uncover novel targets for therapy, Whole-Exome Sequencing (WES) of Anaplastic Lymphoma Kinase (ALK)+ ALCL was performed as well as Gene-Set Enrichment Analysis. This revealed that the T-cell receptor (TCR) and Notch pathways were the most enriched in mutations. In particular, variant T349P of NOTCH1, which confers a growth advantage to cells in which it is expressed, was detected in 12% of ALK+ and ALK- ALCL patient samples. Furthermore, we demonstrate that NPM-ALK promotes NOTCH1 expression through binding of STAT3 upstream of NOTCH1. Moreover, inhibition of NOTCH1 with γ-secretase inhibitors (GSIs) or silencing by shRNA leads to apoptosis; co-treatment in vitro with the ALK inhibitor Crizotinib led to additive/synergistic anti-tumour activity suggesting this may be an appropriate combination therapy for future use in the circumvention of ALK inhibitor resistance. Indeed, Crizotinib-resistant and sensitive ALCL were equally sensitive to GSIs. In conclusion, we show a variant in the extracellular domain of NOTCH1 that provides a growth advantage to cells and confirm the suitability of the Notch pathway as a second-line druggable target in ALK+ ALCL.
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Registered trials
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