ArticleLeukemia2018
NOTCH1 mutations are associated with high CD49d expression in chronic lymphocytic leukemia: link between the NOTCH1 and the NF-κB pathways.
Article in Leukemia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Prognostic significance of in patients with chronic lymphocytic leukemia: A meta-analysis.Annals of hematology · 2025Pooled it
- Resistance pathways and next-generation treatments in chronic lymphocytic leukemia.Discover oncology · 2026Review
- Molecular Features Accompanying Richter's Transformation in Patients with Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2025Review
- CXCR4 overexpression in chronic lymphocytic leukemia associates with poorer prognosis: A prospective, single-center, observational study.Genes and immunity · 2024Observational
- The molecular map of CLL and Richter's syndrome.Seminars in hematology · 2024Review
- CD49d in chronic lymphocytic leukemia: a molecule with multiple regulation layers. Comment to "Sialylation regulates migration in chronic lymphocytic leukemia".Haematologica · 2024Article
- CD49d Expression Identifies a Biologically Distinct Subtype of Chronic Lymphocytic Leukemia with Inferior Progression-Free Survival on BTK Inhibitor Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Treatment Refractoriness in Chronic Lymphocytic Leukemia: Old and New Molecular Biomarkers.International journal of molecular sciences · 2023Review
- NF-kB and the CLL microenvironment.Frontiers in oncology · 2023Review
- Low CD49d expression in newly diagnosed chronic lymphocytic leukaemia may be associated with high-risk features and reduced treatment-free-intervals.European journal of haematology · 2022Article
- Viral transduction of primary human lymphoma B cells reveals mechanisms of NOTCH-mediated immune escape.Nature communications · 2022Article
- 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
- Review
- Multiple Mechanisms of NOTCH1 Activation in Chronic Lymphocytic Leukemia: NOTCH1 Mutations and Beyond.Cancers · 2022Review
- Review
- Impaired nodal shrinkage and apoptosis define the independent adverse outcome of NOTCH1 mutated patients under ibrutinib therapy in chronic lymphocytic leukaemia.Haematologica · 2021Article
- Evaluation of prognostic variables in chronic lymphocytic leukemia and association with disease stage.Molecular and clinical oncology · 2021Article
- Novel pyrrolobenzodiazepine benzofused hybrid molecules inhibit NF-κB activity and synergise with bortezomib and ibrutinib in hematological cancers.Haematologica · 2021Article
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Corrections and comments
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Authors and funding
22 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In chronic lymphocytic leukemia (CLL), stabilizing mutations of NOTCH1, affecting up to 10-15% of cases, have been associated to poor prognosis, disease progression and refractoriness to chemotherapy. NOTCH1 mutations are significantly overrepresented in trisomy 12 CLL, a disease subset frequently expressing CD49d, the α4 chain of the very-late-activation-4 integrin, a well-known key regulator of microenviromental interactions, and negative prognosticator in CLL. In the present study, by analysing a wide cohort of 1180 CLL, we observed a very strong association between the presence of NOTCH1 mutations and the expression of CD49d (P<0.0001), occurring also outside the trisomy 12 CLL subset. Using both the MEC-1 CLL-like cells stably transfected with the NOTCH1 intracellular domain and primary CLL cells bearing a mutated or wild-type NOTCH1 gene configuration, we provide evidence that triggering of the NOTCH1 pathway resulted in a positive CD49d expression regulation, which was driven by a NOTCH1-dependent activation of nuclear factot-κB (NF-κB). Consistently, pharmacological inhibition of the NOTCH1 and/or of the NF-κB pathways resulted in impaired NF-κB nuclear translocation with consequent down-modulation of CD49d expression. Altogether, our data link for the first time NOTCH1 mutations to CD49d expression regulation through the involvement of the NF-κB pathway in CLL.
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