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Lymphoma

Clonal selection in the bone marrow involvement of follicular lymphoma

Leukemia volume 19, pages 1656–1662 (2005)Cite this article

Abstract

To characterize the pathways of bone marrow (BM) involvement of follicular lymphoma (FL), we performed morphological and immunophenotypical analysis of tumor cells from lymph nodes (LNs) and corresponding BMs in 21 patients with FL. In three cases, genealogical trees were constructed based on the immunoglobulin variable region heavy chain (IgVH) gene sequences of tumor clones from LNs and BMs. Results showed that FLs within the BMs display identical or lower cytological grades than in the LNs. In the majority of cases, different proportions of tumor cells expressed bcl-2, CD10 and Ki67 in LNs and BMs. Tumor cells in the BM showed ongoing somatic hypermutation of the IgVH genes; the distribution of these mutations was highly consistent with antigen selection. The topology of the genealogical trees revealed that different subclones populate the LN and BM and BM infiltration may occur at different points of the clonal evolution of FL. Early descendants of the original tumor clone and derivatives of diversified tumor clones may invade the BM. These results suggest that the BM involvement of FL is associated with intensive clonal selection of tumor cells, and the BM provides a microenvironment similar to the germinal centers of LNs, where tumor cells retain their biological nature.

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Acknowledgements

This work was supported by grants from the Hungarian Ministry of Health ETT 144/2003 and from the Hungarian Science Foundation OTKA T032572, T034410, TS49887.

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  1. Á Bognár and B Csernus: These authors contributed equally to this work

Authors and Affiliations

  1. 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary

    Á Bognár, B Csernus, C Bödör, L Reiniger, Á Szepesi, L Kopper & A Matolcsy

  2. Department of Molecular Pathology, National Institute of Oncology, Budapest, Hungary

    E Tóth

  3. Department of Molecular Pathology, Joint Research Organization of the Hungarian Academy of Science and Semmelweis University, Budapest, Hungary

    L Kopper

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  1. Á Bognár
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Correspondence to A Matolcsy.

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Bognár, Á., Csernus, B., Bödör, C. et al. Clonal selection in the bone marrow involvement of follicular lymphoma. Leukemia 19, 1656–1662 (2005). https://doi.org/10.1038/sj.leu.2403844

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