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

Kostas Stamatopoulos, Chrysoula Belessi, Carol Moreno, Myriam Boudjograh, Giuseppe Guida, Tatjana Smilevska, Lynda Belhoul, Stefania Stella, Niki Stavroyianni, Marta Crespo, Anastasia Hadzidimitriou, Laurent Sutton, Francesc Bosch, Nikolaos Laoutaris, Achilles Anagnostopoulos, Emili Montserrat, Athanasios Fassas, Guillaume Dighiero, Federico Caligaris-Cappio, Hélène Merle-BéralPaolo Ghia, Frédéric Davi

Research output: Contribution to journalArticlepeer-review


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)whoexperienced 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.

Original languageEnglish
Pages (from-to)259-270
Number of pages12
Issue number1
Publication statusPublished - Jan 1 2007

ASJC Scopus subject areas

  • Hematology


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