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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
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receptors. _J Clin Invest_ 1998; 102: 1515–1525. Article CAS PubMed PubMed Central Google Scholar Download references ACKNOWLEDGEMENTS This work was supported by grants from both the
KAAD (The Catholic Academic Exchange Service) and the BFS (Bavarian Research Foundation). We thank Professor Andreesen, University of Regensburg Medical Center, Institute of Hematology and
Oncology, and Professor Kreuser, Barmherzige Brüder Hospital, Regensburg, Oncology and Hematology, for providing the patients' samples. Andrea Sassen is acknowledged for her
professional assistance in statistical analysis. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Institute of Pathology, University of Regensburg, Regensburg, Germany M Plander, S Seegers, S
Diermeier-Daucher, F Hofstädter & G Brockhoff * Department of Hematology, County Hospital of Vas, Szombathely, Hungary M Plander & J Iványi * Institute of Clinical Chemistry and
Laboratory Medicine, P Ugocsai, G Schmitz & E Orsó * University of Regensburg, Regensburg, Germany P Ugocsai, G Schmitz & E Orsó * Institute of Pathology, University of Erlangen,
Erlangen, Germany S Schwarz * Institute of Pathology, University Hospital, RWTH Aachen, Aachen, Germany R Knüchel Authors * M Plander View author publications You can also search for this
author inPubMed Google Scholar * S Seegers View author publications You can also search for this author inPubMed Google Scholar * P Ugocsai View author publications You can also search for
this author inPubMed Google Scholar * S Diermeier-Daucher View author publications You can also search for this author inPubMed Google Scholar * J Iványi View author publications You can
also search for this author inPubMed Google Scholar * G Schmitz View author publications You can also search for this author inPubMed Google Scholar * F Hofstädter View author publications
You can also search for this author inPubMed Google Scholar * S Schwarz View author publications You can also search for this author inPubMed Google Scholar * E Orsó View author publications
You can also search for this author inPubMed Google Scholar * R Knüchel View author publications You can also search for this author inPubMed Google Scholar * G Brockhoff View author
publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to G Brockhoff. ADDITIONAL INFORMATION The work was done at the University of
Regensburg, Regensburg, Germany. Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu) SUPPLEMENTARY INFORMATION SUPPLEMENTARY FIGURE 1 (JPG 260
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and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Plander, M., Seegers, S., Ugocsai, P. _et al._ Different proliferative and survival capacity of CLL-cells in a newly established _in
vitro_ model for pseudofollicles. _Leukemia_ 23, 2118–2128 (2009). https://doi.org/10.1038/leu.2009.145 Download citation * Received: 20 October 2008 * Revised: 12 June 2009 * Accepted: 17
June 2009 * Published: 06 August 2009 * Issue Date: November 2009 * DOI: https://doi.org/10.1038/leu.2009.145 SHARE THIS ARTICLE Anyone you share the following link with will be able to read
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KEYWORDS * CLL * pseudofollicles * prognosis * proliferation * thrombocytopenia * apoptosis