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
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