ArticleProceedings of the National Academy of Sciences of the United States of America2016
Oncogenic mutations in the FBXW7 gene of adult T-cell leukemia patients.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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The trial behind it
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
54 citing papers in PubMed, 115 citations in OpenAlex.
- Chidamide inhibits the NOTCH1-MYC signaling axis in T-cell acute lymphoblastic leukemia.Frontiers of medicine · 2022Trial
- Rapid progression of adult T-cell leukemia/lymphoma as tumor-infiltrating Tregs after PD-1 blockade.Blood · 2019Trial
- Rewiring of the Apoptotic Rheostat in HTLV-1 Infection and Adult T-Cell Leukemia/Lymphoma.Cancers · 2026Review
- Expanding clinical variability in FBXW7-related neurodevelopmental disorder: a multicenter case series.Journal of neurodevelopmental disorders · 2026Article
- Exploiting the Notch pathway in HTLV-1-driven adult T-cell leukemia/lymphoma: a mini-review.Annals of hematology · 2026Review
- FBXW7-Related Neurodevelopmental Disorder: Clinical Spectrum, Molecular Mechanisms, and Tumor Predisposition.Human mutation · 2026Review
- Review
- NOTCH1 S2513 is critical for the regulation of NICD levels impacting the segmentation clock in hiPSC-derived PSM cells and somitoids.Genes & development · 2025Article
- Clinical significance of NOTCH1 and FBXW7 alterations in adult T-cell leukemia/lymphoma.International journal of hematology · 2025Article
- Molecular insights and clinical implications for the tumor suppressor role of SCFBiochimica et biophysica acta. Reviews on cancer · 2024Review
- The HTLV-I oncoprotein Tax inactivates the tumor suppressor FBXW7.Journal of virology · 2024Article
- IncreasedInternational journal of molecular sciences · 2024Article
- HTLV-1 Tax Tug-of-War: Cellular Senescence and Death or Cellular Transformation.Pathogens (Basel, Switzerland) · 2024Review
- The Highs and Lows of FBXW7: New Insights into Substrate Affinity in Disease and Development.Cells · 2023Review
- The Role of FBXW7 in Gynecologic Malignancies.Cells · 2023Review
- FBXW7 and human tumors: mechanisms of drug resistance and potential therapeutic strategies.Frontiers in pharmacology · 2023Review
- Circulating microRNAs Suggest Networks Associated with Biological Functions in Aggressive Refractory Type 2 Celiac Disease.Biomedicines · 2022Article
- Clinical significance of FBXW7 loss of function in human cancers.Molecular cancer · 2022Review
- Feedback Loop Regulation between Pim Kinases and Tax Keeps Human T-Cell Leukemia Virus Type 1 Viral Replication in Check.Journal of virology · 2022Article
- Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Human T-cell leukemia virus type 1 (HTLV-I) is associated with adult T-cell leukemia (ATL), an aggressive lymphoproliferative disease with a dismal prognosis. We have previously described the presence of Notch1 activating mutations and constitutive Notch1 signaling in patients with acute ATL. In this study, we report a high frequency of F-box and WD repeat domain containing 7 (FBXW7)/hCDC4 mutations within the WD40 substrate-binding domain in 8 of 32 acute ATL patients (25%). Functionally, ATL FBXW7 mutants lost their ability to interact with intracellular Notch (NICD), resulting in increased protein stability and constitutive Notch1 signaling. Consistent with the loss-of-function found in ATL patients, expression of WT FBXW7 in several patient-derived ATL lines demonstrated strong tumor-suppressor activity characterized by reduced proliferation of ATL cells. Remarkably, two FBXW7 mutants, D510E and D527G, demonstrated oncogenic activity when expressed in the presence of HTLV-I Tax, mutated p53 R276H, or c-Myc F138C found in human cancers. Transforming activity was further demonstrated by the ability of the FBXW7 D510E mutant to provide IL-2-independent growth of Tax-immortalized human T cells and increase the tumor formation in a xenograft mouse model of ATL. This study suggests that FBXW7, normally a tumor suppressor, can act as an oncogene when mutated and may play an important role in the pathogenesis of ATL.
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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.