Mutated V-H genes and preferential V(H)3-21 use define new subsets of mantle cell lymphoma
(2003) In Blood 101(10). p.4047-4054- Abstract
- Mantle cell lymphoma (MCL) is believed to originate from a naive B cell. However, we recently demonstrated that a subset of MCL displayed mutated V-H genes. We also reported restricted use of certain V-H genes. To assess the prognostic impact of these new findings, we performed V-H gene analysis of 110 patients, revealing that 18 (16%) patients had mutated and 92 (84%) patients had unmutated V-H genes. Because the mutation rate was low in the mutated group (2.2%-6.7%), further investigation of the germline V-H gene in T cells from 5 patients with mutated V-H genes was carried out; results showed that the unrearranged V-H gene was identical to the published sequence. These data confirm that the base pair substitutions within the rearranged... (More)
- Mantle cell lymphoma (MCL) is believed to originate from a naive B cell. However, we recently demonstrated that a subset of MCL displayed mutated V-H genes. We also reported restricted use of certain V-H genes. To assess the prognostic impact of these new findings, we performed V-H gene analysis of 110 patients, revealing that 18 (16%) patients had mutated and 92 (84%) patients had unmutated V-H genes. Because the mutation rate was low in the mutated group (2.2%-6.7%), further investigation of the germline V-H gene in T cells from 5 patients with mutated V-H genes was carried out; results showed that the unrearranged V-H gene was identical to the published sequence. These data confirm that the base pair substitutions within the rearranged V-H genes represent hyper-mutations, and indicate germinal center exposure. However, V-H gene mutation status did not correlate with prognosis because there was no difference in clinical outcome between the unmutated and mutated groups. The most frequently used V-H genes were V(H)3-21 (21 patients) and V(H)4-34 (19 patients). A novel finding was that V(H)3-21(+) MCL almost exclusively ex-pressed X light chains and displayed highly restricted use of the V(lambda)3-19 gene. V(H)3-21(+) patients had longer median survival than the remaining patients (53 vs 34 months; P = .03), but they tended to be younger at diagnosis. The combined use Of V(H)3-21/V(lambda)3-19 suggests a possible role for antigen(s) in the pathogenesis of these tumors and indicates that V(H)3-21(+) patients constitute a new MCL entity. (C) 2003 by The American Society of Hematology. (Less)
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https://lup.lub.lu.se/record/312223
- author
- organization
- publishing date
- 2003
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Blood
- volume
- 101
- issue
- 10
- pages
- 4047 - 4054
- publisher
- American Society of Hematology
- external identifiers
-
- wos:000182793000050
- pmid:12637326
- scopus:0037588965
- ISSN
- 1528-0020
- DOI
- 10.1182/blood-2002-11-3479
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Oncology, MV (013035000), Pathology, (Lund) (013030000), Division of Hematology and Transfusion Medicine (013041100)
- id
- ca7a4693-8095-4a4f-8102-39c12bdd53da (old id 312223)
- date added to LUP
- 2016-04-01 11:58:43
- date last changed
- 2022-02-11 00:14:56
@article{ca7a4693-8095-4a4f-8102-39c12bdd53da,
abstract = {{Mantle cell lymphoma (MCL) is believed to originate from a naive B cell. However, we recently demonstrated that a subset of MCL displayed mutated V-H genes. We also reported restricted use of certain V-H genes. To assess the prognostic impact of these new findings, we performed V-H gene analysis of 110 patients, revealing that 18 (16%) patients had mutated and 92 (84%) patients had unmutated V-H genes. Because the mutation rate was low in the mutated group (2.2%-6.7%), further investigation of the germline V-H gene in T cells from 5 patients with mutated V-H genes was carried out; results showed that the unrearranged V-H gene was identical to the published sequence. These data confirm that the base pair substitutions within the rearranged V-H genes represent hyper-mutations, and indicate germinal center exposure. However, V-H gene mutation status did not correlate with prognosis because there was no difference in clinical outcome between the unmutated and mutated groups. The most frequently used V-H genes were V(H)3-21 (21 patients) and V(H)4-34 (19 patients). A novel finding was that V(H)3-21(+) MCL almost exclusively ex-pressed X light chains and displayed highly restricted use of the V(lambda)3-19 gene. V(H)3-21(+) patients had longer median survival than the remaining patients (53 vs 34 months; P = .03), but they tended to be younger at diagnosis. The combined use Of V(H)3-21/V(lambda)3-19 suggests a possible role for antigen(s) in the pathogenesis of these tumors and indicates that V(H)3-21(+) patients constitute a new MCL entity. (C) 2003 by The American Society of Hematology.}},
author = {{Walsh, SH and Thorselius, M and Johnson, Anna and Soderberg, O and Jerkernan, M and Bjorck, E and Eriksson, I and Thunberg, U and Landgren, O and Ehinger, Mats and Lofvenberg, E and Wallman, K and Enblad, G and Sander, B and Porwit-MacDonald, A and Dictor, Michael and Olofsson, Tor and Sundstrom, C and Roos, Gunnel and Rosenquist, R}},
issn = {{1528-0020}},
language = {{eng}},
number = {{10}},
pages = {{4047--4054}},
publisher = {{American Society of Hematology}},
series = {{Blood}},
title = {{Mutated V-H genes and preferential V(H)3-21 use define new subsets of mantle cell lymphoma}},
url = {{http://dx.doi.org/10.1182/blood-2002-11-3479}},
doi = {{10.1182/blood-2002-11-3479}},
volume = {{101}},
year = {{2003}},
}