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Home    Evaluation of the quantitative and functional characteristics of myeloid derived suppressor cells (MDSCs) in patients with chronic lymphocytic leukemia (B-CLL) and associated hypogammaglobulinemia  

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Identifier 000423513
Title Evaluation of the quantitative and functional characteristics of myeloid derived suppressor cells (MDSCs) in patients with chronic lymphocytic leukemia (B-CLL) and associated hypogammaglobulinemia
Alternative Title Προσδιορισμός των ποσοτικών και ποιοτικών χαρακτηριστικών των μυελικών κατασταλτικών κυττάρων σε ασθενείς με χρόνια λεμφοκυτταρική λευχαιμία(Β-ΧΛΛ) και συνοδό υπογαμμασφαιριναιμία
Author Ζαβιτσάνου, Κωνσταντίνα
Thesis advisor Παπαδάκη, Ελένη
Reviewer Ποντίκογλου, Χαράλαμπος
Βενυχάκη, Μαρία
Abstract Chronic lymphocytic leukemia (CLL) is the most common blood cancer among adults in the Western World and is characterized by excessive production of pathological, clonal B-lymphocytes of high CD23, CD5, and CD19 co-expression in peripheral blood, bone marrow and lymph nodes. Hypogammaglobulinemia is a common finding in CLL; it predisposes to infections and exacerbates the complications of the disease. However, the mechanism of its emergence is not well-defined yet. Myeloid Derived Suppressor Cells (MDSCs) are immature cells of myeloid origin, divided into two subpopulations, the polymorphonuclear (PMN)-MDSCs and the monocytic (M)-MDSCs and through various mechanisms they execute their immunosuppressive and tumorigenic function. The aim of the study was to investigate any possible involvement of MDSCs in CLL-associated hypogammaglobulinemia by evaluating their quantitative and functional characteristics. The proportion of PMN-MDSCs and M-MDSCs in untreated CLL patients with and without hypogammaglobulinemia and in healthy individuals was evaluated by flow cytometry in the low-density fraction of the peripheral blood mononuclear cells. Subsequently, the immunosuppressing function of MDSCs was studied by T-cell suppression assays in conditions with and without their presence. The study revealed that CLL patients display significantly increased proportion of peripheral blood PMN-MDSCs and M-MDSCs compared to healthy individuals. This upregulation occurs in patients with both normal and low Ig levels without significant differences for each MDSC subpopulation. Similarly, MDSCs from both CLL patient groups showed a statistically stronger but similar T-lymphocyte suppressive activity compared to MDSCs from healthy subjects. Therefore, MDSCs’ expansion and suppressive function does not represent the main pathogenetic mechanism for the occurrence of hypogammaglobulinemia in CLL. Finally, this study strengthens the connection between MDSCs and CLL and supports the emerging role of these cells as potential biomarkers in malignant-neoplastic diseases.
Language English
Subject Μυελικά κατασταλτικά κύτταρα
Issue date 2019-07-17
Collection   School/Department--School of Medicine--Department of Medicine--Post-graduate theses
  Type of Work--Post-graduate theses
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