ArticleLeukemia2014
Functional impact of NOTCH1 mutations in chronic lymphocytic leukemia.
Article in Leukemia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
- Guidelines for Diagnosis and Treatment of Chronic Lymphocytic Leukemia. Krohem B-Cll 2017.Acta clinica Croatica · 2018Guideline
- Non-coding NOTCH1 mutations in chronic lymphocytic leukemia; their clinical impact in the UK CLL4 trial.Leukemia · 2017Trial
- Trial
- The Role of the Notch1 Signaling Pathway in the Pathogenesis and Treatment of Diabetic Foot: A Review.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2026Review
- ZMYM3 mutations modulate histone acetylation and cooperate with NOTCH1 mutations in chronic lymphocytic leukemia.Blood advances · 2026Article
- Pretreatment With BTK Inhibitors Improved the Sensitivity of DLBCL Cells to CAR-T Cells in a Coculture System by Downregulating the Polarisation of M2 Macrophages.Journal of cellular and molecular medicine · 2026Article
- Rab GTPases drive ligand-independent NOTCH1 activation via altered endocytic trafficking in chronic lymphocytic leukemia.HemaSphere · 2026Article
- Long-read single-cell RNA sequencing enables the study of cancer subclone-specific genotypes and phenotypes in chronic lymphocytic leukemia.Genome research · 2025Article
- Insights into genetic aberrations and signalling pathway interactions in chronic lymphocytic leukemia: from pathogenesis to treatment strategies.Biomarker research · 2024Review
- Multiple omics levels of chronic lymphocytic leukemia.Cell death discovery · 2024Review
- The molecular map of CLL and Richter's syndrome.Seminars in hematology · 2024Review
- Long-read single-cell RNA sequencing enables the study of cancer subclone-specific genotype and phenotype in chronic lymphocytic leukemia.bioRxiv : the preprint server for biology · 2024Article
- CAD204520 TargetsInternational journal of molecular sciences · 2024Article
- Article
- NF-kB and the CLL microenvironment.Frontiers in oncology · 2023Review
- Viral transduction of primary human lymphoma B cells reveals mechanisms of NOTCH-mediated immune escape.Nature communications · 2022Article
- GSK3β is a critical, druggable component of the network regulating the active NOTCH1 protein and cell viability in CLL.Cell death & disease · 2022Article
- Multiple Mechanisms of NOTCH1 Activation in Chronic Lymphocytic Leukemia: NOTCH1 Mutations and Beyond.Cancers · 2022Review
- TGF-β/SMAD Pathway Is Modulated by miR-26b-5p: Another Piece in the Puzzle of Chronic Lymphocytic Leukemia Progression.Cancers · 2022Article
- Multi-platform profiling characterizes molecular subgroups and resistance networks in chronic lymphocytic leukemia.Nature communications · 2021Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The purpose of this study was to compare the expression and function of NOTCH1 in chronic lymphocytic leukemia (CLL) patients harboring a wild-type (WT) or mutated NOTCH1 gene. NOTCH1 mRNA and surface protein expression levels were independent of the NOTCH1 gene mutational status, consistent with the requirement for NOTCH1 signaling in this leukemia. However, compared with NOTCH1-WT CLL, mutated cases displayed biochemical and transcriptional evidence of an intense activation of the NOTCH1 pathway. In vivo, expression and activation of NOTCH1 was highest in CLL cells from the lymph nodes as confirmed by immunohistochemistry. In vitro, the NOTCH1 pathway was rapidly downregulated, suggesting that signaling relies upon micro-environmental interactions even in NOTCH1-mutated cases. Accordingly, co-culture of Jagged1(+) (the NOTCH1 ligand) nurse-like cells with autologous CLL cells sustained NOTCH1 activity over time and mediated CLL survival and resistance against pro-apoptotic stimuli, both abrogated when NOTCH1 signaling was pharmacologically switched off. Together, these results show that NOTCH1 mutations have stabilizing effects on the NOTCH1 pathway in CLL. Furthermore, micro-environmental interactions appear critical in activating the NOTCH1 pathway both in WT and mutated patients. Finally, NOTCH1 signals may create conditions that favor drug resistance, thus making NOTCH1 a potential molecular target in CLL.
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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.