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Numerous Ontogenetic Roads to Mantle Cell Lymphoma: Immunogenetic and Immunohistochemical Evidence
Evangelismos Med Ctr, Hematopathol Dept, Athens, Greece.;Univ Athens, Sch Med, Dept Pathol, Athens, Greece..
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Ctr Res & Technol Hellas CERTH, Inst Appl Biosci, Thessaloniki, Greece.
Evangelismos Med Ctr, Hematopathol Dept, Athens, Greece..
Ctr Res & Technol Hellas CERTH, Inst Appl Biosci, Thessaloniki, Greece..
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2017 (English)In: American Journal of Pathology, ISSN 0002-9440, E-ISSN 1525-2191, Vol. 187, no 7, 1454-1458 p.Article in journal (Refereed) Published
Abstract [en]

To obtain insight into the ontogeny of mantle cell lymphoma (MCL), we assessed 206 patients from a morphological, immunohistochemical, and immunogenetic perspective. Our series included nodal (n = 151), extranodal. (n = 28), and primary splenic (n = 27) MCL cases. Skewing of the immunoglobulin heavy variable (IGHV) gene repertoire was noted, with only four IGHV genes accounting for 46% of cases and approximately 70% of cases (107/154) bearing an imprint of somatic hypermutation (SHM) ranging from minimalto pronounced. Interestingly, a distinctive immunophenotypic and immunogenetic profile was identified for primary splenic MCL, which was enriched for DBA.44-positive cases (P < 0.001) and used the IGHV1-8 gene more frequently (P = 0.02) compared to nodal or extranodal cases, alluding to distinct immunopathogenetic and antigen selection processes. Expression of CD27 (considered a marker of activated B cells) was generally dissociated from SHM and was more prevalent in cases with no or minimal/borderline SHM. These findings support the idea that antigen drive is relevant for most MCL cases, although the specific antigens and the precise location of affinity maturation remain to be elucidated. Moreover, they raise the intriguing hypothesis of multiple cellular origins for MCL.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC , 2017. Vol. 187, no 7, 1454-1458 p.
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-328974DOI: 10.1016/j.ajpath.2017.02.017ISI: 000404320500003PubMedID: 28457696OAI: oai:DiVA.org:uu-328974DiVA: diva2:1140614
Available from: 2017-09-12 Created: 2017-09-12 Last updated: 2017-09-12Bibliographically approved

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Sundström, ChristerStamatopoulos, Kostas

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Science for Life Laboratory, SciLifeLabDepartment of Immunology, Genetics and Pathology
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