Plander, M and Seegers, Silvia and Ugocsai, P and Diermeier-Daucher, S and Iványi, J and Schmitz, G and Hofstädter, F and Schwarz, S and Orsó, E and Knüchel, R and Brockhoff, G
Different proliferative and survival capacity of CLL-cells in a newly established in vitro model for pseudofollicles.
Leukemia 23 (11), pp. 2118-2128.
Other URL: http://www.nature.com/leu/journal/v23/n11/full/leu2009145a.html
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.
|Date:||6 August 2009|
|Institutions:|| Medicine > Lehrstuhl für Pathologie|
|Aged, 80 and over||MESH|
|Cell Culture Techniques/methods||MESH|
|Leukemia, Lymphocytic, Chronic, B-Cell/pathology||MESH|
|Subjects:||600 Technology > 610 Medical sciences Medicine|
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Yes|
|Deposited On:||14 Feb 2011 12:43|
|Last Modified:||21 Jul 2011 02:06|