L-Selectin Expression is Influenced by Phosphatase Activity in Chronic Lymphocytic Leukemia

Ildikó Beke Debreceni, Róbert Szász, Zoltán Kónya, Ferenc Erdődi, Flóra Kiss, János Kappelmayer

Research output: Contribution to journalArticle

Abstract

Background: 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. Methods: 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). Results: 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. Conclusions: 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.

Original languageEnglish
Pages (from-to)149-157
Number of pages9
JournalCytometry Part B - Clinical Cytometry
Volume96
Issue number2
DOIs
Publication statusPublished - Mar 2019

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Keywords

  • L-selectin expression
  • chronic lymphocytic leukemia
  • protein phosphatases
  • soluble L-selectin
  • tumor necrosis factor alpha converting enzyme

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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