ArticleLeukemia2016
NOTCH1 mutations associate with low CD20 level in chronic lymphocytic leukemia: evidence for a NOTCH1 mutation-driven epigenetic dysregulation.
Article in Leukemia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 87 citations in OpenAlex.
- Article
- Advancing the therapeutic effectiveness of paclitaxel in chronic lymphocytic leukemia through the simultaneous inhibition of NOTCH1 and SF3B1.Cancer cell international · 2025Article
- Article
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- Treatment Refractoriness in Chronic Lymphocytic Leukemia: Old and New Molecular Biomarkers.International journal of molecular sciences · 2023Review
- Article
- High-resolution Melting Analysis for NOTCH1 c.7541-7542delCT Mutation in Chronic Lymphocytic Leukemia: Prognostic Significance in Egyptian Patients.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2022Article
- Multiple Mechanisms of NOTCH1 Activation in Chronic Lymphocytic Leukemia: NOTCH1 Mutations and Beyond.Cancers · 2022Review
- Article
- NOTCH1 Signalling: A key pathway for the development of high-risk chronic lymphocytic leukaemia.Frontiers in oncology · 2022Review
- Role of Notch2 pathway in mature B cell malignancies.Frontiers in oncology · 2022Review
- Article
- Impaired nodal shrinkage and apoptosis define the independent adverse outcome of NOTCH1 mutated patients under ibrutinib therapy in chronic lymphocytic leukaemia.Haematologica · 2021Article
- Challenges with Approved Targeted Therapies against Recurrent Mutations in CLL: A Place for New Actionable Targets.Cancers · 2021Review
- Chronic Lymphocytic Leukemia.Cold Spring Harbor perspectives in medicine · 2021Review
- Therapeutic Options for Patients with TP53 Deficient Chronic Lymphocytic Leukemia: Narrative Review.Cancer management and research · 2021Review
- Clinical Features and Prognostic Significance ofFrontiers in oncology · 2021Article
- A step ahead toward precision medicine for chronic lymphocytic leukemia.Haematologica · 2020Article
- A laboratory-based scoring system predicts early treatment in Rai 0 chronic lymphocytic leukemia.Haematologica · 2020Article
- The regulation and function of CD20: an "enigma" of B-cell biology and targeted therapy.Haematologica · 2020Review
Corrections and comments
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Authors and funding
22 authors at 9 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In chronic lymphocytic leukemia (CLL), NOTCH1 mutations have been associated with clinical resistance to the anti-CD20 rituximab, although the mechanisms behind this peculiar behavior remain to be clarified. In a wide CLL series (n=692), we demonstrated that CLL cells from NOTCH1-mutated cases (87/692) were characterized by lower CD20 expression and lower relative lysis induced by anti-CD20 exposure in vitro. Consistently, CD20 expression by CLL cells was upregulated in vitro by γ-secretase inhibitors or NOTCH1-specific small interfering RNA and the stable transfection of a mutated (c.7541-7542delCT) NOTCH1 intracellular domain (NICD-mut) into CLL-like cells resulted in a strong downregulation of both CD20 protein and transcript. By using these NICD-mut transfectants, we investigated protein interactions of RBPJ, a transcription factor acting either as activator or repressor of NOTCH1 pathway when respectively bound to NICD or histone deacetylases (HDACs). Compared with controls, NICD-mut transfectants had RBPJ preferentially complexed to NICD and showed higher levels of HDACs interacting with the promoter of the CD20 gene. Finally, treatment with the HDAC inhibitor valproic acid upregulated CD20 in both NICD-mut transfectants and primary CLL cells. In conclusion, NOTCH1 mutations are associated with low CD20 levels in CLL and are responsible for a dysregulation of HDAC-mediated epigenetic repression of CD20 expression.
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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.