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Proliferation centers in chronic lymphocytic leukemia: the niche where NF-κB activation takes place

Leukemia volume 24, pages 872–876 (2010)Cite this article

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Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is characterized by the slow accumulation of small, mature B cells and prolymphocytes that typically display the CD5, CD19, CD23 and CD20 markers. CLL/SLL cells suffer spontaneous apoptosis in vitro. However, they are rescued when cultured with follicular dendritic cells, other dendritic cells or with a CD40-ligand (CD154)-expressing fibroblast cell line. Furthermore, it has been demonstrated that CLL/SLL cells are protected from apoptosis by their interaction with nurse-like cells, a subset of blood monocytes described in the spleen of CLL/SLL patients that express vimentin and stromal-derived factor 1 (SDF1), together with high levels of CD14 and CD68.1 Thus, evidence is accumulating that the defective apoptosis of CLL/SLL B cells can be ascribed not only to intrinsic defects of the neoplastic cells, but also to extrinsic factors in the microenvironment that influence their behavior.2, 3

CLL/SLL lymph node infiltration has a distinctive characteristic, the presence of pseudofollicles or proliferation centers (PCs), which are more rarely described in the white pulp of the spleen and the bone marrow. PCs are newly formed structures, and have not been described in reactive lymphadenitis or other lymphoproliferative conditions. They contain a pool of proliferating cells that appear as vaguely nodular areas that can be recognized against a monotonous background of small mature-looking lymphocytes because they are clearly visible at low magnification.4 PCs contain a continuum of small, medium and large cells consisting of prolymphocytes, which are small to medium-sized cells with relatively clumped chromatin and small nucleoli, and paraimmunoblasts, which are larger cells with round to oval nuclei, dispersed chromatin, central eosinophilic nucleoli and slightly basophilic cytoplasm. PCs have been proposed as being the site for B cell receptor signaling, and B cells within PCs have been shown to express IRF4, suggesting that PC morphology may reflect important biological features of this neoplasm. Nevertheless, these anatomical structures are not observed in lymph nodes of the existing CLL/SLL mouse models, which makes it difficult to address their functional relevance.

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Acknowledgements

This study was supported by the Instituto de Salud Carlos III (RETICS, FIS PI052742, PI052800, INT07/028, Acción Transversal) and the Ministerio de Ciencia e Innovación (SAF2005-00221, SAF2008-03871), Spain.

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Author notes

  1. B Herreros and S M Rodríguez-Pinilla: These authors contributed equally to this work.

Authors and Affiliations

  1. Lymphoma Group, Molecular Pathology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain

    B Herreros, S M Rodríguez-Pinilla, S Montes-Moreno, M Sánchez-Beato & M Á Piris

  2. Histology and Immunohistochemistry Core Unit, Biotechnology Programme, CNIO, Madrid, Spain

    R Pajares, M Lozano & L Sánchez-Verde

  3. Pathology Department, Hospital 12 de Octubre, Madrid, Spain

    M Á Martínez-Gónzalez

  4. Monoclonal Antibody Unit, Biotechnology Programme, CNIO, Madrid, Spain

    R Ramos & G Roncador

  5. Human Genetics Group, Human Cancer Genetics Programme, CNIO, Madrid, Spain

    I Munoz

  6. Pathology Department, Hospital de Txagorritsu, Vitoria, Álava, Spain

    R D de Otazu

  7. Pathology Department, Hospital Santa María del Rosell, Cartagena, Murcia, Spain

    M Pérez-Guillermo

  8. Pathology Department, Hospital de Móstoles, Madrid, Spain

    M J Mestre

  9. Pathology Department, Hospital Puerta de Hierro, Madrid, Spain

    C Bellas

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  1. B Herreros
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Corresponding author

Correspondence to S M Rodríguez-Pinilla.

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Herreros, B., Rodríguez-Pinilla, S., Pajares, R. et al. Proliferation centers in chronic lymphocytic leukemia: the niche where NF-κB activation takes place. Leukemia 24, 872–876 (2010). https://doi.org/10.1038/leu.2009.285

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