ArticleHaematologica2016
SLP76 integrates into the B-cell receptor signaling cascade in chronic lymphocytic leukemia cells and is associated with an aggressive disease course.
Article in Haematologica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- LCP2 mediates SUV39H1-driven cellular senescence-related chemoresistance in natural killer/T-cell lymphoma.Cell death & disease · 2026Article
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- A Novel Peptide that Disrupts the Lck-IPArchives of microbiology & immunology · 2023Article
- Identification of useful biomolecular markers in kidney renal clear cell carcinoma: an in silico and in vitro analysis-based study.American journal of translational research · 2023Article
- Identification of prognostic biomarkers associated with tumor microenvironment in ceRNA network for esophageal squamous cell carcinoma: a bioinformatics study based on TCGA database.Discover oncology · 2021Article
- Lymphocyte cytosolic protein 2 is a novel prognostic marker in lung adenocarcinoma.The Journal of international medical research · 2021Article
- A novel prognostic biomarker LCP2 correlates with metastatic melanoma-infiltrating CD8Scientific reports · 2021Article
- Identification of a tumor microenvironment-related gene signature to improve the prediction of cervical cancer prognosis.Cancer cell international · 2021Article
- Epigenetic programming underpins B-cell dysfunction in peanut and multi-food allergy.Clinical & translational immunology · 2021Article
- Transcriptome-Based Network Analysis Unveils Eight Immune-Related Genes as Molecular Signatures in the Immunomodulatory Subtype of Triple-Negative Breast Cancer.Frontiers in oncology · 2020Article
- Beyond TCR Signaling: Emerging Functions of Lck in Cancer and Immunotherapy.International journal of molecular sciences · 2019Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
I In the last decade, the B-cell receptor has emerged as a pivotal stimulus in the pathogenesis of chronic lymphocytic leukemia, and a very feasible therapeutic target in this disease. B-cell receptor responsiveness in chronic lymphocytic leukemia cells is heterogeneous among patients and correlates with aggressiveness of the disease. Here we show, for the first time, that SLP76, a key scaffold protein in T-cell receptor signaling, is ectopically expressed in chronic lymphocytic leukemia cells, with variable levels among patients, and correlates positively with unmutated immunoglobulin heavy chain variable gene status and ZAP-70 expression. We found that SLP76 was functionally active in chronic lymphocytic leukemia cells. A SYK-dependent basal level of phosphorylated SLP76 exists in the cells, and upon B-cell receptor engagement, SLP76 tyrosine phosphorylation is significantly enhanced concomitantly with increased physical association with BTK. B-cell receptor-induced SLP76 phosphorylation is mediated by upstream signaling events involving LCK and SYK. Knockdown of SLP76 in the cells resulted in decreased induction of BTK, PLCγ2 and IκB phosphorylation, as well as cell viability after B-cell receptor activation with anti-IgM. Consistent with our biochemical findings, high total SLP76 expression in chronic lymphocytic leukemia cells correlated with a more aggressive disease course. IN
conclusionSLP76 is ectopically expressed in chronic lymphocytic leukemia cells where it plays a role in B-cell receptor signaling.
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