Pathogenetic role of BCL6 translocation in B-cell non-Hodgkin's lymphoma.
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 B-NHL 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.
Ohno
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Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. hohno@k2.dion.ne.jp
D001483:Base Sequence; D002875:Chromosomes / Q000648:ultrastructure; D002893:Chromosomes, Human, Pair 3; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000378:metabolism*; D008957:Models, Genetic; D021381:Protein Transport; D051560:Proto-Oncogene Proteins c-bcl-6; D011995:Recombination, Genetic; D014178:Translocation, Genetic
C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; D051560:Proto-Oncogene Proteins c-bcl-6