Computational identification of CDR3 sequence archetypes among immunoglobulin sequences in chronic lymphocytic leukemia

Bradley T. Messmer, Benjamin J. Raphael, Sarah J. Aerni, George F. Widhopf, Laura Z. Rassenti, John G. Gribben, Neil E. Kay, Thomas J. Kipps

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The leukemia cells of unrelated patients with chronic lymphocytic leukemia (CLL) display a restricted repertoire of immunoglobulin (Ig) gene rearrangements with preferential usage of certain Ig gene segments. We developed a computational method to rigorously quantify biases in Ig sequence similarity in large patient databases and to identify groups of patients with unusual levels of sequence similarity. We applied our method to sequences from 1577 CLL patients through the CLL Research Consortium (CRC), and identified 67 similarity groups into which roughly 20% of all patients could be assigned. Immunoglobulin light chain class was highly correlated within all groups and light chain gene usage was similar within sets. Surprisingly, over 40% of the identified groups were composed of somatically mutated genes. This study significantly expands the evidence that antigen selection shapes the Ig repertoire in CLL.

Original languageEnglish (US)
Pages (from-to)368-376
Number of pages9
JournalLeukemia Research
Volume33
Issue number3
DOIs
StatePublished - Mar 2009

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology
  • Cancer Research

Keywords

  • Immunoglobulin sequence
  • Leukemia
  • Light chain

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