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Molecular genetic characterization reveals new subsets of mantle cell lymphoma

Molecular genetic characterization reveals new subsets of mantle cell lymphoma Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy, which is believed to originate from naïve B-cells in the mantle zone of lymph nodes. Recently, a more diverse cellular origin has been implicated in MCL, since the disease was shown to consist of two subsets based on immunoglobulin heavy-chain variable (IGHV) gene analysis; a major subset with unmutated IGHV genes and a smaller subset (∼20 to 30%) displaying mutated IGHV genes. Presence of somatic hypermutation in the ‘mutated’ subset suggests either exposure to a germinal centre (GC) environment or that somatic hypermutation has been acquired in a non-GC context. Furthermore, a preferential IGHV gene utilization has been revealed in MCL, where IGHV3-21 and IGHV4-34 are the most predominant. MCLs with an IGHV3-21 usage almost exclusively share the same light chain (IGLV3-19) use and this subset is also related to a better prognosis. MCL cases utilising the IGHV3-21 gene display less chromosomal alterations than MCLs using other IGHV genes and in addition, gains in 15q and losses in 9p were not observed in any of these cases. These latter findings are in favour of the hypothesis that IGHV3-21+ tumours may represent a distinct MCL subentity and that there is a possible role for antigens in MCL development. In this review, we will summarise these recent studies of IG gene rearrangements in MCL as well as molecular cytogenetic characteristics of this malignancy. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Leukemia & Lymphoma Taylor & Francis

Molecular genetic characterization reveals new subsets of mantle cell lymphoma

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References (67)

Publisher
Taylor & Francis
Copyright
© 2008 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted
ISSN
1029-2403
eISSN
1042-8194
DOI
10.1080/10428190801947559
pmid
18452063
Publisher site
See Article on Publisher Site

Abstract

Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy, which is believed to originate from naïve B-cells in the mantle zone of lymph nodes. Recently, a more diverse cellular origin has been implicated in MCL, since the disease was shown to consist of two subsets based on immunoglobulin heavy-chain variable (IGHV) gene analysis; a major subset with unmutated IGHV genes and a smaller subset (∼20 to 30%) displaying mutated IGHV genes. Presence of somatic hypermutation in the ‘mutated’ subset suggests either exposure to a germinal centre (GC) environment or that somatic hypermutation has been acquired in a non-GC context. Furthermore, a preferential IGHV gene utilization has been revealed in MCL, where IGHV3-21 and IGHV4-34 are the most predominant. MCLs with an IGHV3-21 usage almost exclusively share the same light chain (IGLV3-19) use and this subset is also related to a better prognosis. MCL cases utilising the IGHV3-21 gene display less chromosomal alterations than MCLs using other IGHV genes and in addition, gains in 15q and losses in 9p were not observed in any of these cases. These latter findings are in favour of the hypothesis that IGHV3-21+ tumours may represent a distinct MCL subentity and that there is a possible role for antigens in MCL development. In this review, we will summarise these recent studies of IG gene rearrangements in MCL as well as molecular cytogenetic characteristics of this malignancy.

Journal

Leukemia & LymphomaTaylor & Francis

Published: Jan 1, 2008

Keywords: Mantle cell lymphoma; immunoglobulin genes; somatic hypermutation; IGHV3-21 gene usage; genomic imbalances; array-CGH

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