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Mutated V-H genes and preferential V(H)3-21 use define new subsets of mantle cell lymphoma

Walsh, SH; Thorselius, M; Johnson, Anna LU ; Soderberg, O; Jerkernan, M; Bjorck, E; Eriksson, I; Thunberg, U; Landgren, O and Ehinger, Mats LU , et al. (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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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
id
ca7a4693-8095-4a4f-8102-39c12bdd53da (old id 312223)
date added to LUP
2007-09-24 07:04:55
date last changed
2018-10-03 10:14:19
@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},
  volume       = {101},
  year         = {2003},
}