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Stereotyped patterns of somatic hypermutation in subsets of patients with chronic lymphocytic leukemia: implications for the role of antigen selection in leukemogenesis

Murray, Fiona; Darzentas, Nikos; Hadzidimitriou, Anastasia; Tobin, Gerard; Boudjogra, Myriarn; Scielzo, Cristina; Laoutaris, Nikolaos; Karlsson, Karin LU ; Baran-Marzsak, Fanny and Tsaftaris, Athanasios, et al. (2008) In Blood 111(3). p.1524-1533
Abstract
Somatic hypermutation (SHM) features in a series of 1967 immunoglobulin heavy chain gene (IGH) rearrangements obtained from patients with chronic lymphocytic leukemia (CLL) were examined and compared with IGH sequences from non-CLL B cells available in public databases. SHM analysis was performed for all 1290 CLL sequences in this cohort with less than 100% identity to germ line. At the cohort level, SHM patterns were typical of a canonical SHM process. However, important differences emerged from the analysis of certain subgroups of CLL sequences defined by: (1) IGHV gene usage, (2) presence of stereotyped heavy chain complementarity-determining region 3 (HCDR3) sequences, and (3) mutational load. Recurrent, "stereotyped" amino acid... (More)
Somatic hypermutation (SHM) features in a series of 1967 immunoglobulin heavy chain gene (IGH) rearrangements obtained from patients with chronic lymphocytic leukemia (CLL) were examined and compared with IGH sequences from non-CLL B cells available in public databases. SHM analysis was performed for all 1290 CLL sequences in this cohort with less than 100% identity to germ line. At the cohort level, SHM patterns were typical of a canonical SHM process. However, important differences emerged from the analysis of certain subgroups of CLL sequences defined by: (1) IGHV gene usage, (2) presence of stereotyped heavy chain complementarity-determining region 3 (HCDR3) sequences, and (3) mutational load. Recurrent, "stereotyped" amino acid changes occurred across the entire IGHV region in CLL subsets carrying stereotyped HCDR3 sequences, especially those expressing the IGHV3-21 and IGHV4-34 genes. These mutations are un-derrepresented among non-CLL sequences and thus can be considered as CLL-biased. Furthermore, it was shown that even a low level of mutations may be functionally relevant, given that stereotyped amino acid changes can be found in subsets of minimally mutated cases. The precise targeting and distinctive features of somatic hypermutation (SHM) in selected subgroups of CLL patients provide further evidence for selection by specific antigenic element(s). (Less)
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subject
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Blood
volume
111
issue
3
pages
1524 - 1533
publisher
American Society of Hematology
external identifiers
  • wos:000252792900083
  • scopus:38949203770
ISSN
1528-0020
DOI
10.1182/blood-2007-07-099564
language
English
LU publication?
yes
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6396738a-f4a1-487e-b4fc-0cd03388b0d6 (old id 1198815)
date added to LUP
2008-09-10 17:10:17
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2017-08-13 03:46:56
@article{6396738a-f4a1-487e-b4fc-0cd03388b0d6,
  abstract     = {Somatic hypermutation (SHM) features in a series of 1967 immunoglobulin heavy chain gene (IGH) rearrangements obtained from patients with chronic lymphocytic leukemia (CLL) were examined and compared with IGH sequences from non-CLL B cells available in public databases. SHM analysis was performed for all 1290 CLL sequences in this cohort with less than 100% identity to germ line. At the cohort level, SHM patterns were typical of a canonical SHM process. However, important differences emerged from the analysis of certain subgroups of CLL sequences defined by: (1) IGHV gene usage, (2) presence of stereotyped heavy chain complementarity-determining region 3 (HCDR3) sequences, and (3) mutational load. Recurrent, "stereotyped" amino acid changes occurred across the entire IGHV region in CLL subsets carrying stereotyped HCDR3 sequences, especially those expressing the IGHV3-21 and IGHV4-34 genes. These mutations are un-derrepresented among non-CLL sequences and thus can be considered as CLL-biased. Furthermore, it was shown that even a low level of mutations may be functionally relevant, given that stereotyped amino acid changes can be found in subsets of minimally mutated cases. The precise targeting and distinctive features of somatic hypermutation (SHM) in selected subgroups of CLL patients provide further evidence for selection by specific antigenic element(s).},
  author       = {Murray, Fiona and Darzentas, Nikos and Hadzidimitriou, Anastasia and Tobin, Gerard and Boudjogra, Myriarn and Scielzo, Cristina and Laoutaris, Nikolaos and Karlsson, Karin and Baran-Marzsak, Fanny and Tsaftaris, Athanasios and Moreno, Carol and Anagnostopoulos, Achilles and Caligaris-Cappio, Federico and Vaur, Dominique and Ouzounis, Christos and Belessi, Chrysoula and Ghia, Paolo and Davi, Fred and Rosenquist, Richard and Stamatopoulos, Kostas},
  issn         = {1528-0020},
  language     = {eng},
  number       = {3},
  pages        = {1524--1533},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Stereotyped patterns of somatic hypermutation in subsets of patients with chronic lymphocytic leukemia: implications for the role of antigen selection in leukemogenesis},
  url          = {http://dx.doi.org/10.1182/blood-2007-07-099564},
  volume       = {111},
  year         = {2008},
}