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Progressive immunoglobulin gene mutations in chronic lymphocytic leukemia: evidence for antigen-driven intraclonal diversification.

Publication ,  Journal Article
Volkheimer, AD; Weinberg, JB; Beasley, BE; Whitesides, JF; Gockerman, JP; Moore, JO; Kelsoe, G; Goodman, BK; Levesque, MC
Published in: Blood
February 15, 2007

Somatic mutations of immunoglobulin genes characterize mature memory B cells, and intraclonal B-cell diversification is typically associated with expansion of B-cell clones with greater affinity for antigen (antigen drive). Evidence for a role of antigen in progression of intraclonal chronic lymphocytic leukemia (CLL) cell diversification in patients with mutated immunoglobulin genes has not been previously presented. We performed a single-cell analysis of immunoglobulin heavy and light chains in 6 patients with somatically mutated CLL-cell immunoglobulin genes and identified 2 patients with multiple related (oligoclonal) subgroups of CLL cells. We constructed genealogic trees of these oligoclonal CLL-cell subgroups and assessed the effects of immunoglobulin somatic mutations on the ratios of replacement and silent amino acid changes in the framework and antigen-binding regions (CDRs) of the immunoglobulin heavy and light chains from each oligoclonal CLL-cell population. In one subject, the amino acid changes were consistent with an antigen-driven progression of clonally related CLL-cell populations. In the other subject, intraclonal diversification was associated with immunoglobulin amino acid changes that would have likely lessened antigen affinity. Taken together, these studies support the hypothesis that in some CLL cases intraclonal diversification is dependent on antigen interactions with immunoglobulin receptors.

Duke Scholars

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Published In

Blood

DOI

ISSN

0006-4971

Publication Date

February 15, 2007

Volume

109

Issue

4

Start / End Page

1559 / 1567

Location

United States

Related Subject Headings

  • Receptors, Fc
  • Mutation
  • Middle Aged
  • Male
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Immunology
  • Immunoglobulin Light Chains
  • Immunoglobulin Heavy Chains
  • Humans
  • Genes, Immunoglobulin
 

Citation

APA
Chicago
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MLA
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Volkheimer, A. D., Weinberg, J. B., Beasley, B. E., Whitesides, J. F., Gockerman, J. P., Moore, J. O., … Levesque, M. C. (2007). Progressive immunoglobulin gene mutations in chronic lymphocytic leukemia: evidence for antigen-driven intraclonal diversification. Blood, 109(4), 1559–1567. https://doi.org/10.1182/blood-2006-05-020644
Volkheimer, Alicia D., J Brice Weinberg, Bethany E. Beasley, John F. Whitesides, Jon P. Gockerman, Joseph O. Moore, Garnett Kelsoe, Barbara K. Goodman, and Marc C. Levesque. “Progressive immunoglobulin gene mutations in chronic lymphocytic leukemia: evidence for antigen-driven intraclonal diversification.Blood 109, no. 4 (February 15, 2007): 1559–67. https://doi.org/10.1182/blood-2006-05-020644.
Volkheimer AD, Weinberg JB, Beasley BE, Whitesides JF, Gockerman JP, Moore JO, et al. Progressive immunoglobulin gene mutations in chronic lymphocytic leukemia: evidence for antigen-driven intraclonal diversification. Blood. 2007 Feb 15;109(4):1559–67.
Volkheimer, Alicia D., et al. “Progressive immunoglobulin gene mutations in chronic lymphocytic leukemia: evidence for antigen-driven intraclonal diversification.Blood, vol. 109, no. 4, Feb. 2007, pp. 1559–67. Pubmed, doi:10.1182/blood-2006-05-020644.
Volkheimer AD, Weinberg JB, Beasley BE, Whitesides JF, Gockerman JP, Moore JO, Kelsoe G, Goodman BK, Levesque MC. Progressive immunoglobulin gene mutations in chronic lymphocytic leukemia: evidence for antigen-driven intraclonal diversification. Blood. 2007 Feb 15;109(4):1559–1567.

Published In

Blood

DOI

ISSN

0006-4971

Publication Date

February 15, 2007

Volume

109

Issue

4

Start / End Page

1559 / 1567

Location

United States

Related Subject Headings

  • Receptors, Fc
  • Mutation
  • Middle Aged
  • Male
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Immunology
  • Immunoglobulin Light Chains
  • Immunoglobulin Heavy Chains
  • Humans
  • Genes, Immunoglobulin