ArticleLeukemia2017
Mutations in NOTCH1 PEST domain orchestrate CCL19-driven homing of chronic lymphocytic leukemia cells by modulating the tumor suppressor gene DUSP22.
Article in Leukemia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 65 citations in OpenAlex.
- Discovery of Candidate DNA Methylation Cancer Driver Genes.Cancer discovery · 2021Trial
- Functional cooperation between the B-cell receptor and NOTCH1 in regulating metabolic reprogramming in chronic lymphocytic leukemia.Leukemia · 2026Article
- IGHV1 usage is associated with lymphadenopathy and aggressive disease in the TCL1 mouse model for chronic lymphocytic leukemia.Scientific reports · 2025Article
- Molecular Mechanisms in the Transformation from Indolent to Aggressive B Cell Malignancies.Cancers · 2025Review
- Optical genome mapping with whole genome sequencing identifies complex chromosomal structural variations in acute leukemia.Frontiers in genetics · 2025Article
- The molecular map of CLL and Richter's syndrome.Seminars in hematology · 2024Review
- CRISPR-Cas9 in basic and translational aspects of cancer therapy.BioImpacts : BI · 2024Review
- The Role of Methylation in Chronic Lymphocytic Leukemia and Its Prognostic and Therapeutic Impacts in the Disease: A Systematic Review.Advances in hematology · 2024Review
- Article
- Periconceptional folate intake influences DNA methylation at birth based on dietary source in an analysis of pediatric acute lymphoblastic leukemia cases and controls.The American journal of clinical nutrition · 2022Article
- Genomic landscape of mature B-cell non-Hodgkin lymphomas - an appraisal from lymphomagenesis to drug resistance.Journal of the Egyptian National Cancer Institute · 2022Review
- Viral transduction of primary human lymphoma B cells reveals mechanisms of NOTCH-mediated immune escape.Nature communications · 2022Article
- Hepatocyte phosphatase DUSP22 mitigates NASH-HCC progression by targeting FAK.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
- Multiple Mechanisms of NOTCH1 Activation in Chronic Lymphocytic Leukemia: NOTCH1 Mutations and Beyond.Cancers · 2022Review
- PTEN/PI3K/Akt pathway alters sensitivity of T-cell acute lymphoblastic leukemia to L-asparaginase.Scientific reports · 2022Article
- From Descriptive to Functional Genomics of Leukemias Focusing on Genome Engineering Techniques.International journal of molecular sciences · 2021Review
- Biological significance of monoallelic and biallelic BIRC3 loss in del(11q) chronic lymphocytic leukemia progression.Blood cancer journal · 2021Article
- Challenges with Approved Targeted Therapies against Recurrent Mutations in CLL: A Place for New Actionable Targets.Cancers · 2021Review
- Dual-Specificity Phosphatase 15 (DUSP15) Modulates Notch Signaling by Enhancing the Stability of Notch Protein.Molecular neurobiology · 2021Article
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Even if NOTCH1 is commonly mutated in chronic lymphocytic leukemia (CLL), its functional impact in the disease remains unclear. Using CRISPR/Cas9-generated Mec-1 cell line models, we show that NOTCH1 regulates growth and homing of CLL cells by dictating expression levels of the tumor suppressor gene DUSP22. Specifically, NOTCH1 affects the methylation of DUSP22 promoter by modulating a nuclear complex, which tunes the activity of DNA methyltransferase 3A (DNMT3A). These effects are enhanced by PEST-domain mutations, which stabilize the molecule and prolong signaling. CLL patients with a NOTCH1-mutated clone showed low levels of DUSP22 and active chemotaxis to CCL19. Lastly, in xenograft models, NOTCH1-mutated cells displayed a unique homing behavior, localizing preferentially to the spleen and brain. These findings connect NOTCH1, DUSP22, and CCL19-driven chemotaxis within a single functional network, suggesting that modulation of the homing process may provide a relevant contribution to the unfavorable prognosis associated with NOTCH1 mutations in CLL.
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Registered trials
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