B-cell receptor epitope recognition correlates with the clinical course of chronic lymphocytic leukemia

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Blank B-cell receptor epitope recognition correlates with the clinical course of

chronic lymphocytic leukemia.

M Binder, F Muller, A Jackst, B Lechenne, M Pantic, U Bacher, CZ Eulenburg, H

Veelken, R Mertelsmann, R Pasqualini, W Arap, and M Trepel

Cancer, November 29, 2010; .

Department of Oncology and Hematology, Hubertus Wald Cancer Center, University

Medical Center, Hamburg-Eppendorf, Hamburg, Germany.

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. Cancer 2010. ? 2010 American Cancer Society.

PMID: 21117166