Transformation of follicular lymphoma to diffuse large B-cell lymphoma may occur by divergent evolution from a common progenitor cell or by direct evolution from the follicular lymphoma clone

To investigate the cell of origin linking follicular (FL) and transformed (t-FL) lymphomas, we analyzed the somatic hypermutation (SHM) pattern of the variable region of the immunoglobulin heavy gene (IgH-VH) in 18 sequential FL/t-FL samples and a father (donor) and son (recipient), who developed FL...

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Bibliographic Details
Published in:Blood 2009-04, Vol.113 (15), p.3553-3557
Main Authors: Carlotti, Emanuela, Wrench, David, Matthews, Janet, Iqbal, Sameena, Davies, Andrew, Norton, Andrew, Hart, Jason, Lai, Raymond, Montoto, Silvia, Gribben, John G., Lister, T. Andrew, Fitzgibbon, Jude
Format: Article
Language:English
Subjects:
Biological and medical sciences
Biopsy
Bone Marrow Transplantation
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - immunology
Clone Cells - immunology
Clone Cells - pathology
Germinal Center - pathology
Hematologic and hematopoietic diseases
Humans
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Lymphoma, Follicular - genetics
Lymphoma, Follicular - pathology
Lymphoma, Follicular - therapy
Lymphoma, Large B-Cell, Diffuse - genetics
Lymphoma, Large B-Cell, Diffuse - pathology
Male
Medical sciences
Somatic Hypermutation, Immunoglobulin
Stem Cells - immunology
Stem Cells - pathology
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Summary:To investigate the cell of origin linking follicular (FL) and transformed (t-FL) lymphomas, we analyzed the somatic hypermutation (SHM) pattern of the variable region of the immunoglobulin heavy gene (IgH-VH) in 18 sequential FL/t-FL samples and a father (donor) and son (recipient), who developed FL and t-FL, after transplantation. Genealogic trees showed a pattern compatible with a common progenitor cell (CPC) origin in 13 cases. The identification of the t-FL clonotype in the previous FL sample and of the putative CPC sequence in both the FL/t-FL biopsies showed that the intraclonal diversity of FL and t-FL germinal centers (GCs) is more intricate than previously described, and all 3 clonotypes (CPC, FL, t-FL) may occur simultaneously within the same lymph node. On the basis of the father/son model, this CPC must be long-lived, providing a possible explanation for the incurable nature of this disease.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2008-08-174839