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Laser microdissection for the assessment of the clonal relationship between chronic lymphocytic leukemia/small lymphocytic lymphoma and proliferating B cells within lymph node pseudofollicles

Leukemia volume 25, pages 883–888 (2011)Cite this article

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Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a disease characterized by the progressive accumulation of monoclonal CD5+, CD19+ and CD23+ B-cells in the blood, lymphoid tissues and marrow. Because nearly all CLL/SLL cells in the blood are in G0/G1 phase of the cell cycle, it has been assumed that CLL/SLL was due to the slow accumulation of incompetent lymphocytes that cannot normally undergo apoptosis. However, isotopic labeling of the CLL/SLL cells in vivo revealed that CLL/SLL is rather a dynamic process with high rates of leukemia cell turnover, often at levels exceeding 0.1–1.75% of the entire CLL/SLL clone per day.1 Given that a CLL/SLL clone contains between 1012 and 1014 cells, this high rate of turnover implies that some patients might generate ∼109 to 1012 CLL/SLL cells each day. This has led to speculation that there must be at least two compartments for CLL/SLL, one in which quiescent, leukemia B cells might accumulate, such as the blood, and another comprised of proliferating B cells that might be housed in the marrow and/or secondary lymphoid tissues of patients with this disease.2

Increasingly, the proliferating compartment is posted to exist within pseudofollicles, which can be found in secondary lymphoid tissues of patients with CLL/SLL. Such pseudofollicles contain stromal cells, T cells and B cells, which express markers associated with activation and proliferation, for example, Ki-67, and the anti-apoptotic protein survivin, a member of the inhibitor of apoptosis family considered to have a role in promoting leukemia cell survival.3 Immunohistochemical investigations of these pseudofollicles have revealed many properties in common with reactive B-cell follicles, suggesting that they may be centers of antigen-driven proliferation.4 Because these pseudofollicles are assumed to contain proliferating leukemia B cells, increasingly they have been designated as proliferation centers for CLL/SLL.

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Acknowledgements

The Research was funded by a PhD grant from the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen) to Mado Vandewoestyne and Valerie Pede and supported by two grants from the Fund for Scientific Research in Flanders (FWO-Vlaanderen) one awarded to the laboratory of Pharmaceutical Biotechnology and one to the Department of Clinical Chemistry, Microbiology and Immunology (Grant No. G.0991.10N).

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Authors and Affiliations

  1. Laboratory for Pharmaceutical Biotechnology, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium

    M L Vandewoestyne, M F Dhaenens & D L Deforce

  2. Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, Ghent, Belgium

    V C Pede & J J Philippé

  3. Department of Pathology, N Goormaghtigh Institute, Ghent University Hospital, Ghent, Belgium

    K Y Lambein & M M Praet

  4. Department of Hematology, Ghent University Hospital, Ghent, Belgium

    F C Offner

  5. Department of Medicine, Moores Cancer Center, University of California at San Diego, La Jolla, USA

    T J Kipps

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  1. M L Vandewoestyne
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Correspondence to D L Deforce.

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Vandewoestyne, M., Pede, V., Lambein, K. et al. Laser microdissection for the assessment of the clonal relationship between chronic lymphocytic leukemia/small lymphocytic lymphoma and proliferating B cells within lymph node pseudofollicles. Leukemia 25, 883–888 (2011). https://doi.org/10.1038/leu.2011.14

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