Media type: E-Article Title: L‐Selectin Expression is Influenced by Phosphatase Activity in Chronic Lymphocytic Leukemia Contributor: Beke Debreceni, Ildikó; Szász, Róbert; Kónya, Zoltán; Erdődi, Ferenc; Kiss, Flóra; Kappelmayer, János imprint: Wiley, 2019 Published in: Cytometry Part B: Clinical Cytometry Language: English DOI: 10.1002/cyto.b.21771 ISSN: 1552-4949; 1552-4957 Keywords: Cell Biology ; Histology ; Pathology and Forensic Medicine Origination: Footnote: Description: <jats:sec><jats:title>Background</jats:title><jats:p>Adhesion receptors have important role in cellular invasiveness and L‐selectin is a primary determinant in the binding of chronic lymphocytic leukemia (CLL) cells to several glycated proteins on endothelial cells. We investigated L‐selectin expression on CLL cells and explored the mechanisms that lead to their shedding.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Surface and soluble L‐selectin expression levels were studied by flow cytometry and immunoassay, respectively. Magnetically isolated B‐cells from patients and controls were investigated for total and protein phosphatase‐2A activities. Flow cytometry of permeabilized cells was utilized for the determination of phosphorylated mitogen‐activated protein kinase (pp38MAPK) and surface tumor necrosis factor alpha‐converting enzyme expression (TACE).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In CLL patients elevated absolute lymphocyte cell counts, high soluble and low surface L‐selectin expression were observed. Similarly, TACE surface expression was significantly lower on B‐CLL cells compared to normal B‐cells. Both total phosphatase and protein phosphatase‐2A activities were also significantly lower in B‐CLL cells compared to normal B‐cells and we found a consequently higher level of pp38 MAPK in B‐CLL cells. Based on in vitro experiments a MAPK inhibitor could attenuate the phosphatase inhibitor's effect on L‐selectin shedding.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The lower phosphatase activity detectable in chronic lymphocytic leukemia, results in a downstream signaling cascade with subsequent reduction of surface L‐selectin expression and this effect is mediated by enhanced phosphorylation of p38MAPK and an altered TACE expression. © 2019 The Authors. <jats:italic>Cytometry Part B: Clinical Cytometry</jats:italic> published by Wiley Periodicals, Inc. on behalf of International Clinical Cytometry Society.</jats:p></jats:sec> Access State: Open Access