title: B-cell receptor epitope recognition correlates with the clinical course of chronic lymphocytic leukemia.
abstract: BACKGROUND
  B-cell receptors (BCRs) and their recognition of specific epitopes may play a pivotal role in the development and progression of chronic lymphocytic leukemia (CLL). In this study, the authors set up a model system to explore epitope reactivity and its clinical relevance in CLL.
  
  
  METHODS
  Epitope-mimicking peptides were selected from phage display libraries on 6 CLL BCRs from randomly chosen patients. The binding of the 6 index epitope mimics was evaluated in a set of 100 unrelated CLL samples. Epitope recognition patterns were correlated with the clinical course of the disease.
  
  
  RESULTS
  Surprisingly, all CLL samples recognized 1 or several index epitopes, and some revealed marked polyreactivity. Patients with CLL who expressed BCRs that reacted with ≥5 epitope mimics had a significantly worse clinical course than less polyreactive patients (median time to first treatment, 24 months vs 102 months). This effect was independent of otherwise known prognostic markers.
  
  
  CONCLUSIONS
  The authors introduced a system with which to model epitope reactivity of CLL BCRs without previous knowledge of potential antigens. The findings indicated that a polyreactive epitope recognition pattern may be a determinant of an aggressive clinical course in this disease. This further emphasizes the functional and prognostic relevance of BCR epitope recognition in CLL.
authors.affiliation: Department of Oncology and Hematology, Hubertus Wald Cancer Center, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Mascha
authors.initials: M
authors.lastname: Binder
authors.forename: Fabian
authors.initials: F
authors.lastname: Müller
authors.forename: Antje
authors.initials: A
authors.lastname: Jackst
authors.forename: Barbara
authors.initials: B
authors.lastname: Léchenne
authors.forename: Milena
authors.initials: M
authors.lastname: Pantic
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bacher
authors.forename: Christine
authors.initials: C
authors.lastname: Zu Eulenburg
authors.forename: Hendrik
authors.initials: H
authors.lastname: Veelken
authors.forename: Roland
authors.initials: R
authors.lastname: Mertelsmann
authors.forename: Renata
authors.initials: R
authors.lastname: Pasqualini
authors.forename: Wadih
authors.initials: W
authors.lastname: Arap
authors.forename: Martin
authors.initials: M
authors.lastname: Trepel
mesh_terms: D018450:Disease Progression; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000473:pathology; D019151:Peptide Library; D011947:Receptors, Antigen, B-Cell / Q000276:immunology
chemical_list: D018985:Epitopes, B-Lymphocyte; D019151:Peptide Library; D011947:Receptors, Antigen, B-Cell