Clonal selection in the bone marrow involvement of follicular lymphoma

• Published in: Leukemia Vol. 19; no. 9; pp. 1656 - 1662
• Main Authors: BOGNSR, A, CSERNUS, B, BÖDÖR, C, REINIGER, L, SZEPESI, A, TOTH, E, KOPPER, L, MATOLCSY, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01-09-2005; Nature Publishing Group
• Subjects: Antigens; Bcl-2 protein; Biological and medical sciences; Bone marrow; Bone Marrow - immunology; Bone Marrow - pathology; Clonal selection; Clone Cells; Cloning; DNA Mutational Analysis; Gene sequencing; Germinal centers; Hematologic and hematopoietic diseases; Humans; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Variable Region - genetics; Immunophenotyping; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymph nodes; Lymph Nodes - immunology; Lymph Nodes - pathology; Lymphoma; Lymphoma, Follicular - diagnosis; Lymphoma, Follicular - genetics; Lymphoma, Follicular - immunology; Medical sciences; Metastases; Microenvironments; Mutation; Phylogeny; Polymerase Chain Reaction; Sequence Analysis, DNA - methods; Somatic hypermutation; Topology; Trees; Tumor cells; Tumors; Variable region; somatic hypermutation; Hematology; Lymphoproliferative syndrome; Follicular lymphoma; Bone marrow; Clonal selection; Malignant hemopathy; Non Hodgkin lymphoma; bone marrow involvement
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2403844

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 (IgV(H)) 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 IgV(H) 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.