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Immunoglobulin gene segment usage, location and immunogenicity in mutated and unmutated chronic lymphocytic leukaemia
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
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2005 (English)In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 129, no 4, 499-510 p.Article in journal (Refereed) Published
Abstract [en]

The mutational status of the variable region of the immunoglobulin heavy chain gene (IgV(H)) is an important prognostic marker in B-cell chronic lymphocytic leukaemia (B-CLL), with mutated patients having improved outcome. To examine the impact of mutational status on V(H), D(H), and J(H) gene segment location and immunogenicity, we analysed 375 IgH sequences from 356 patients with B-CLL. Although V(H) and D(H) gene usage was different in mutated compared to unmutated patients, there was no impact of gene location on frequency of use or clinical outcome. Surprisingly, somatic mutations did not increase the immunogenicity of the Ig, as assessed by predicted binding affinity of Ig-derived peptides to major histocompatibility Class I and Class II molecules. Even excluding patients using V(H)1-69, cases using the V(H)1 gene family had a poor outcome. Both mutated and unmutated CLL patients demonstrated evidence of antigen selection. The worst outcome was seen in the subset of 14 unmutated patients with similar HCDR3 amino acid sequence using V(H)1-69, D(H)3-3 and J(H)6, suggesting an antigen-driven process modulating the clinical course.

Place, publisher, year, edition, pages
Blackwell Publishing, 2005. Vol. 129, no 4, 499-510 p.
Keyword [en]
chronic lymphocytic leukaemia, V(H)D(H)J(H) gene usage, HCDR3, antigen selection, MHC binding affinity
National Category
Hematology
Identifiers
URN: urn:nbn:se:umu:diva-22958DOI: 10.1111/j.1365-2141.2005.05480.xISI: 000228965400005PubMedID: 15877732OAI: oai:DiVA.org:umu-22958DiVA: diva2:218745
Available from: 2009-05-20 Created: 2009-05-20 Last updated: 2017-12-13Bibliographically approved

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