Pathogenetic role of BCL6 translocation in B-cell non-Hodgkin’s lymphoma
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H. Ohno [1]
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[1] Kyoto University
Kyoto University
Kamigyō-ku, Japón
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- Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 19, Nº. 2, 2004, págs. 637-650
- Idioma: inglés
- Enlaces
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Resumen
Chromosomal translocation affecting the 3q27 band, where the BCL6 gene is localized, is one of the most common genetic abnormalities in non- Hodgkin’s lymphoma of B-cell type (B-NHL). The translocation occurs within the major translocation cluster (MTC) of BCL6, and as the result of translocation either one of the three immunoglobulin (Ig) genes or a heterogeneous non-Ig gene is juxtaposed to the coding regions of BCL6. On the other hand, somatic hypermutation involves the BCL6 gene of not only BNHL but also B-cells from normal individuals. The mutations are clustered within a region of the MTC, suggesting that a common molecular mechanism is operating for the two genetic lesions of BCL6. The Bcl-6 protein is a transcriptional repressor that is an important regulator of lymphoid development and function. The protein is preferentially expressed in germinal center (GC) B-cells of normal lymphoid tissues as well as in a variety of B-NHL subtypes derived from GC B-cells irrespective of whether the BCL6 is rearranged. Although there is no consensus on the effect of BCL6 translocation on the clinical outcome of B-NHL, many studies coincide in showing that a high-level of BCL6 expression at either or both the mRNA and protein levels is a favorable prognostic marker of diffuse large B-cell lymphoma. In vitro evidence suggests that non-Ig/BCL6 translocation transiently enhances the level of Bcl-6 expression, which may perturb a molecular network that controls the differentiation of GC B-cells to Ig-secreting plasma cells, thereby predisposing the B-cells to neoplastic transformation.
