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Lymphoma

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

Leukemia volume 23, pages 2118–2128 (2009)Cite this article

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.

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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.

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Authors and Affiliations

  1. Institute of Pathology, University of Regensburg, Regensburg, Germany

    M Plander, S Seegers, S Diermeier-Daucher, F Hofstädter & G Brockhoff

  2. Department of Hematology, County Hospital of Vas, Szombathely, Hungary

    M Plander & J Iványi

  3. Institute of Clinical Chemistry and Laboratory Medicine,

    P Ugocsai, G Schmitz & E Orsó

  4. University of Regensburg, Regensburg, Germany

    P Ugocsai, G Schmitz & E Orsó

  5. Institute of Pathology, University of Erlangen, Erlangen, Germany

    S Schwarz

  6. Institute of Pathology, University Hospital, RWTH Aachen, Aachen, Germany

    R Knüchel

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Correspondence to G Brockhoff.

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The work was done at the University of Regensburg, Regensburg, Germany.

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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

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