ArticleScientific reports2017
Lck is a relevant target in chronic lymphocytic leukaemia cells whose expression variance is unrelated to disease outcome.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Transcriptomic and proteomic differences in BTK-WT and BTK-mutated CLL and their changes during therapy with pirtobrutinib.Blood advances · 2024Article
- A Novel Peptide that Disrupts the Lck-IPArchives of microbiology & immunology · 2023Article
- Integrated signaling and transcriptome analysis reveals Src family kinase individualities and novel pathways controlled by their constitutive activity.Frontiers in immunology · 2023Article
- Integrative and Comprehensive Pan-Cancer Analysis of Lymphocyte-Specific Protein Tyrosine Kinase in Human Tumors.International journal of molecular sciences · 2022Article
- Role of Programmed Cell Death Protein-1 and Lymphocyte Specific Protein Tyrosine Kinase in the Aryl Hydrocarbon Receptor- Mediated Impairment of the IgM Response in Human CD5Frontiers in immunology · 2022Article
- New horizons in drug discovery of lymphocyte-specific protein tyrosine kinase (Lck) inhibitors: a decade review (2011-2021) focussing on structure-activity relationship (SAR) and docking insights.Journal of enzyme inhibition and medicinal chemistry · 2021Review
- LCK and CD3E Orchestrate the Tumor Microenvironment and Promote Immunotherapy Response and Survival of Muscle-Invasive Bladder Cancer Patients.Frontiers in cell and developmental biology · 2021Article
- Genetic Loss of LCK Kinase Leads to Acceleration of Chronic Lymphocytic Leukemia.Frontiers in immunology · 2020Article
- Beyond TCR Signaling: Emerging Functions of Lck in Cancer and Immunotherapy.International journal of molecular sciences · 2019Review
- Lymphocyte-Specific Protein Tyrosine Kinase (LCK) is Involved in the Aryl Hydrocarbon Receptor-Mediated Impairment of Immunoglobulin Secretion in Human Primary B Cells.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- Ectopic Lck expression in CLL demarcates intratumoral subpopulations with aberrant B-cell receptor signaling.Blood advances · 2018Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Pathogenesis of chronic lymphocytic leukaemia (CLL) is contingent upon antigen receptor (BCR) expressed by malignant cells of this disease. Studies on somatic hypermutation of the antigen binding region, receptor expression levels and signal capacity have all linked BCR on CLL cells to disease prognosis. Our previous work showed that the src-family kinase Lck is a targetable mediator of BCR signalling in CLL cells, and that variance in Lck expression associated with ability of BCR to induce signal upon engagement. This latter finding makes Lck similar to ZAP70, another T-cell kinase whose aberrant expression in CLL cells also associates with BCR signalling capacity, but also different because ZAP70 is not easily pharmacologically targetable. Here we describe a robust method of measuring Lck expression in CLL cells using flow cytometry. However, unlike ZAP70 whose expression in CLL cells predicts prognosis, we find Lck expression and disease outcome in CLL are unrelated despite observations that its inhibition produces effects that biologically resemble the egress phenotype taken on by CLL cells treated with idelalisib. Taken together, our findings provide insight into the pathobiology of CLL to suggest a more complex relationship between expression of molecules within the BCR signalling pathway and disease outcome.
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