Over 20% of patients with chronic lymphocytic leukemia carry stereotyped receptors: Pathogenetic implications and clinical correlations

Blood. 2007 Jan 1;109(1):259-70. doi: 10.1182/blood-2006-03-012948. Epub 2006 Sep 19.

Abstract

The chronic lymphocytic leukemia (CLL) immunoglobulin repertoire is biased and characterized by the existence of subsets of cases with closely homologous ("stereotyped") complementarity-determining region 3 (CDR3) sequences. In the present series, 201 (21.9%) of 916 patients with CLL expressed IGHV genes that belonged to 1 of 48 different subsets of sequences with stereotyped heavy chain (H) CDR3. Twenty-six subsets comprised 3 or more sequences and were considered "confirmed." The remaining subsets comprised pairs of sequences and were considered "potential"; public database CLL sequences were found to be members of 9 of 22 "potential" subsets, thereby allowing us to consider them also "confirmed." The chance of belonging to a subset exceeded 35% for unmutated or selected IGHV genes (eg, IGHV1-69/3-21/4-39). Comparison to non-CLL public database sequences showed that HCDR3 restriction is "CLL-related." CLL cases with selected stereotyped immunoglobulins (IGs) were also found to share unique biologic and clinical features. In particular, cases expressing stereotyped IGHV4-39/IGKV1-39-1D-39 and IGHV4-34/IGKV2-30 were always IgG-switched. In addition, IGHV4-34/IGKV2-30 patients were younger and followed a strikingly indolent disease, contrasting other patients (eg, those expressing IGHV3-21/IGLV3-21) who experienced an aggressive disease, regardless of IGHV mutations. These findings suggest that a particular antigen-binding site can be critical in determining the clinical features and outcome for at least some CLL patients.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / analysis
  • Amino Acid Sequence
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / pathology
  • Base Sequence
  • Cohort Studies
  • Epitopes
  • Follow-Up Studies
  • France
  • Gene Frequency
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain*
  • Genes, Immunoglobulin*
  • Greece
  • Humans
  • Immunoglobulin Class Switching
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin Switch Region*
  • Immunoglobulin Variable Region / genetics*
  • Italy
  • Leukemia, Lymphocytic, Chronic, B-Cell / etiology
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology*
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Rheumatoid Factor / immunology
  • Sequence Homology
  • Somatic Hypermutation, Immunoglobulin*
  • Spain

Substances

  • Epitopes
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Rheumatoid Factor
  • ADP-ribosyl Cyclase 1