Different proliferative and survival capacity of CLL-cells in a newly established in vitro model for pseudofollicles
Autor: | Peter Ugocsai, J. Iványi, Simone Diermeier-Daucher, Márk Plander, Silvia Seegers, Evelyn Orsó, Stephan Schwarz, Ferdinand Hofstädter, Ruth Knüchel, G. Brockhoff, Gerd Schmitz |
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Rok vydání: | 2009 |
Předmět: |
Male
Cancer Research Interleukin-10/pharmacology Chronic lymphocytic leukemia Interleukin-4/pharmacology Cell Culture Techniques 610 Medizin Cell Culture Techniques/methods Apoptosis Stromal Cells/cytology Immunophenotyping Bone Marrow immune system diseases hemic and lymphatic diseases Thrombocytopenia/pathology Aged 80 and over Cell Survival/physiology ddc:610 biology Leukemia Lymphocytic Chronic B-Cell/pathology Anemia/pathology Anemia Cell Differentiation Apoptosis/physiology Hematology Middle Aged Prognosis Interleukin-10 Haematopoiesis Leukemia Oncology Female Stem cell Cell Division Adult Stromal cell Cell Survival CD40 Ligand Cell Division/physiology medicine Cell Differentiation/physiology Humans Culture Media/pharmacology Aged CD40 business.industry Bone marrow failure medicine.disease Leukemia Lymphocytic Chronic B-Cell Thrombocytopenia Culture Media CD40 Ligand/pharmacology Bone Marrow/pathology Immunology biology.protein Interleukin-2 Interleukin-4 Stromal Cells business Interleukin-2/pharmacology |
DOI: | 10.5283/epub.19599 |
Popis: | Chronic lymphocytic leukemia (CLL) is a malignancy of mature B-lymphocytes that manifests in a variety of clinical courses. The accumulation of CLL-cells is primarily caused by defective apoptosis; however, a higher proliferative capacity has also been found to correlate with poorer prognostic factors. Proliferating CLL-cells are confined to specialized structures called pseudofollicles, which contain CLL-cells, T-lymphocytes, and stromal cells. We established an in vitro model for pseudofollicles to characterize the behavior of CLL-cells in relation to clinical courses with different outcomes. Only CLL-cells from progressive clinical cases were inducible to proliferate by a combination of soluble CD40L/IL-2/IL-10 in co-culture with stromal cells. Proliferating CLL-cells showed a higher and more extensive expression of antigens, which are important in T-B-cell interactions such as CD40, MHC II, and adhesion molecules. IL-4 increased interferon regulatory factor-4 expression and induced a specific immunophenotype, which may imply plasmacytic differentiation. Furthermore, it was shown that co-cultured stromal cells protected CLL-cells from apoptosis. CLL-cells from clinically indolent cases had a far worse survival rate in medium than the cells from poor prognostic cases. Thus, we can assume that not only a different resistance to apoptosis, but also proliferation contributes to the progression of CLL resulting in bone marrow failure with thrombocytopenia and anemia. |
Databáze: | OpenAIRE |
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