Molecular evidence for EBV and CMV persistence in a subset of patients with chronic lymphocytic leukemia expressing stereotyped IGHV4-34 B-cell receptors

E. Kostareli, A. Hadzidimitriou, N. Stavroyianni, N. Darzentas, A. Athanasiadou, M. Gounari, V. Bikos, A. Agathagelidis, T. Touloumenidou, I. Zorbas, A. Kouvatsi, N. Laoutaris, A. Fassas, A. Anagnostopoulos, C. Belessi, K. Stamatopoulos

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Abstract

The chronic lymphocytic leukemia (CLL) immunoglobulin repertoire is uniquely characterized by the presence of stereotyped B-cell receptors (BCRs). A major BCR stereotype in CLL is shared by immunoglobulin G-switched cases utilizing the immunoglobulin heavy-chain variable 4-34 (IGHV4-34) gene. Increased titers of IGHV4-34 antibodies are detected in selective clinical conditions, including infection by B-cell lymphotropic viruses, particularly Epstein-Barr virus (EBV) and cytomegalovirus (CMV). In this context, we sought evidence for persistent activation by EBV and CMV in CLL cases expressing the IGHV4-34 gene. The study group included 93 CLL cases with an intentional bias for the IGHV4-34 gene. On the basis of real-time PCR results for CMV/EBV DNA, cases were assigned to three groups: (1) double-negative (59/93); (2) single-positive (CMV- or EBV-positive; 25/93); (3) double-positive (9/93). The double-negative group was characterized by heterogeneous IGHV gene repertoire. In contrast, a bias for the IGHV4-34 gene was observed in the single-positive group (9/25 cases; 36%). Remarkably, all nine double-positive cases utilized the IGHV4-34 gene; seven of nine cases expressed the major BCR stereotype as described above. In conclusion, our findings indicate that the interactions of CLL progenitor cells expressing distinctive IGHV4-34 BCRs with viral antigens/superantigens might facilitate clonal expansion and, eventually, leukemic transformation. The exact type, timing and location of these interactions remain to be determined.

Original languageEnglish
Pages (from-to)919-924
Number of pages6
JournalLeukemia
Volume23
Issue number5
DOIs
Publication statusPublished - 2009

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ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Kostareli, E., Hadzidimitriou, A., Stavroyianni, N., Darzentas, N., Athanasiadou, A., Gounari, M., Bikos, V., Agathagelidis, A., Touloumenidou, T., Zorbas, I., Kouvatsi, A., Laoutaris, N., Fassas, A., Anagnostopoulos, A., Belessi, C., & Stamatopoulos, K. (2009). Molecular evidence for EBV and CMV persistence in a subset of patients with chronic lymphocytic leukemia expressing stereotyped IGHV4-34 B-cell receptors. Leukemia, 23(5), 919-924. https://doi.org/10.1038/leu.2008.379