Dokument: Biological role of the expression of tumor necrosis factor receptor-ligand family molecules on acute leukemia cells
| Titel: | Biological role of the expression of tumor necrosis factor receptor-ligand family molecules on acute leukemia cells | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=2699 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20040112-000699-1 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Glouchkova, Ludmila [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Göbel, Ulrich [Gutachter] Prof. Dr. Mehlhorn, Hans-Peter Heinz [Gutachter] Prof. Dr. Dilloo, Dagmar [Gutachter] | |||||||
| Stichwörter: | Leukämie, B-Zellen, kostimulatorische Moleküle, Immunotherapie, Apoptosisleukemia, B-cells, immunotherapy, costimulation, apoptose | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
| Beschreibung: | The characterization of important molecules expressed on leukemias cells has allowed a further understanding of basic biologic mechanisms including apoptosis pathways or immune responses directed against individual malignant cell. For generation of leukemia cell vaccines the manipulation of the expression-level of costimulatory molecules for achieving the most efficient T-cell stimulation, or of CD95 expression for enhanced apoptosis of leukemia cells seem to be promising targets. The aim of the present work is to study the biological role of the expression of the tumor necrosis factor receptor-ligand family molecules such as costimulatory molecules CD70-CD27 and apoptosis-mediating CD95 molecule on ALL cells. In this work, the importance of the CD70-CD27 costimulatory pathway involved in antigenpresentation was investigated in primary ALL cells that have been stimulated in vitro by CD40L expressing feeder cells. By flow-cytometry analysis it was found that expression of CD70 could be significantly enhanced after CD40-stimulation. The importance of the CD70- CD27 pathway for ALL cells was characterized here for the first time to synergistically enhance the CD80/CD86-CD28 mediated antigen presentation. In addition, using a protocol for in vitro generation of T-cell lines it was demonstrated that the CD70-CD27 pathway is a prerequisite for generation of cytotoxic T cells (CTL). For the first time the expression of costimulatory molecules and their clinical relevance were investigated on the large number of primary blasts from newly diagnosed patients with ALL. It was found that high CD27 expression rate correlates with patients belonging to the low risk group. It has been shown, that ALL cells up-regulated CD95 at high level after CD40-stimulation and demonstrated sensitivity toward CD95-mediated apoptosis. Moreover, the CD95-mediated apoptosis in CD40-stimulated ALL blasts can be enhanced by cycloheximide-treatment most likely due to blockade of anti-apoptotic proteins. More important, it was found that high level of CD95 on CD40-stimulated ALL blasts and their sensitivity to CD95-mediated apoptosis are associated with low risk prognosis. Since the design of efficient leukemia vaccine is based on the enhancement of reduced tumorgenicity of leukemia cells, a deeper understanding of the molecules and mechanisms that are responsible for the induction of the immunogenicity of leukemia cells can have implication for the immunotherapy of ALL. The data observed here for ALL are encouraging for up-coming clinical trials of leukemia vaccines. | |||||||
| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät » WE Biologie | |||||||
| Dokument erstellt am: | 12.01.2004 | |||||||
| Dateien geändert am: | 12.02.2007 | |||||||
| Promotionsantrag am: | 01.12.2003 | |||||||
| Datum der Promotion: | 01.12.2003 |
