Different proliferative and survival capacity of CLL-cells in a newly established in vitro model for pseudofollicles

Plander, M. and Seegers, S. and Ugocsai, P. and Diermeier-Daucher, S. and Ivanyi, J. and Schmitz, G. and Hofstaedter, F. and Schwarz, S. and Orso, E. and Knuechel, R. and Brockhoff, Gero (2009) Different proliferative and survival capacity of CLL-cells in a newly established in vitro model for pseudofollicles. LEUKEMIA, 23 (11). pp. 2118-2128. ISSN 0887-6924, 1476-5551

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Abstract

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. Leukemia (2009) 23, 2118-2128; doi: 10.1038/leu.2009.145; published online 6 August 2009

Item Type: Article
Uncontrolled Keywords: CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELL; PLASMA-CELLS; CHEMOKINE RECEPTORS; T-CELLS; EXPRESSION; APOPTOSIS; LYMPHOMA; DISEASE; CD40; CLL; pseudofollicles; prognosis; proliferation; thrombocytopenia; apoptosis
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin
Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 02 Sep 2020 13:27
Last Modified: 02 Sep 2020 13:27
URI: https://pred.uni-regensburg.de/id/eprint/28217

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