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-6proto-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.
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Acknowledgements
We would like to thank Teresa Tavilla and Laura Veroni for excellent secretarial assistance. This work has been supported by grants from: AIRC, Milan, Italy and Ministero della Sanità, Progetti Finalizati, Rome, Italy (to MF); ‘Fondazione Piera Pietro e Giovanni Ferrero’, Alba, Italy and ‘Fondazione CRT’, Torino, Italy (to GG). DC is being supported by a fellowship from AIRC, Milan, Italy. Grant No. AI 10811 (to NC).
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Capello, D., Fais, F., Vivenza, D. et al. Identification of three subgroups of B cell chronic lymphocytic leukemia based upon mutations of BCL-6 and IgV genes. Leukemia 14, 811–815 (2000). https://doi.org/10.1038/sj.leu.2401766
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DOI: https://doi.org/10.1038/sj.leu.2401766
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