Identification of three subgroups of B cell chronic lymphocytic leukemia based upon mutations of BCL-6 and lgV genes

D. Capello, F. Fais, D. Vivenza, G. Migliaretti, N. Chiorazzi, G. Gaidano, M. Ferrarini

Research output: Contribution to journalArticle

Abstract

Although B cell chronic lymphocytic leukemia (B-CLL) has been traditionally viewed as a tumor of virgin B cells, this notion has been recently questioned by data suggesting that a fraction of B-CLL derives from antigen experienced B cells. In order to further clarify the histogenetic derivation of this lymphoproliferation, we have analyzed the DNA sequences of the 5' non-coding region of BCL-6 proto-oncogene in 28 cases of B-CLL. Mutations of BCL-6 proto-oncogene, a zinc finger transcription factor implicated in lymphoma development, represent a histogenetic marker of B cell transit through the germinal center (GC) and occur frequently in B cell malignancies derived from GC or post-GC B cells. For comparison, the same tumor panel was analyzed for somatic mutations of the rearranged immunoglobulin variable (IgV) genes, which are known to be acquired at the time of B cell transit through the GC. Sequence analyses of BCL-6 and IgV genes allowed the definition of three groups of B-CLL. Group I B-CLL displayed mutations of both BCL-6 and IgV genes (10/28; 36%). Group II B-CLL displayed mutated IgV genes, but a germline BCL-6 gene (5/28; 18%). Finally, group III B-CLL included the remaining cases (13/28; 46%) that were characterized by the absence of somatic mutations of both BCL-6 and IgV genes. Overall, the distribution of BCL-6 and IgV mutations in B-CLL reinforce the notion that this leukemia is histogenetically heterogeneous and that a substantial subgroup of these lymphoproliferations derives from post-germinal center B cells.

Original languageEnglish
Pages (from-to)811-815
Number of pages5
JournalLeukemia
Volume14
Issue number5
Publication statusPublished - 2000

    Fingerprint

Keywords

  • BCL-6
  • Chronic lymphocytyc leukemia
  • Immunoglobulin variable region
  • Somatic mutation

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Capello, D., Fais, F., Vivenza, D., Migliaretti, G., Chiorazzi, N., Gaidano, G., & Ferrarini, M. (2000). Identification of three subgroups of B cell chronic lymphocytic leukemia based upon mutations of BCL-6 and lgV genes. Leukemia, 14(5), 811-815.