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Lymphoma

The BCL6 gene in B-cell lymphomas with 3q27 translocations is expressed mainly from the rearranged allele irrespective of the partner gene

Leukemia volume 17, pages 1390–1397 (2003)Cite this article

Abstract

The BCL6 gene, which functions as a transcription repressor, is the target of multiple chromosomal translocations in non-Hodgkin's lymphomas (NHL). These translocations occur in the nontranslated region of the BCL6 gene, juxtaposing regulatory sequences of the diverse partner genes to the open reading frame of the BCL6 gene and thus are thought to deregulate BCL6 gene expression. The levels of expression of the BCL6 gene and protein have been demonstrated to predict the clinical outcome of diffuse large B-cell lymphomas. By contrast, the prognostic significance of BCL6 gene translocations is unclear. In this study we have sought an explanation for this apparent discrepancy. We examined tumors with a variety of different BCL6 translocations and therefore with a variety of potentially substituted promoters. We found no increase in total BCL6 mRNA levels in the NHL specimens harboring BCL6 gene translocation. Indeed, some of these tumors expressed relatively low quantities of the BCL6 mRNA. We also sought to determine whether BCL6 transcription occurs from the rearranged or from the normal untranslocated allele in these tumors. We demonstrate that lymphoma cell lines and majority of NHL tumor specimens expressed BCL6 mRNA predominantly from the rearranged allele that may come under the control of various partner gene promoters. However, few NHL tumors with BCL6 gene translocations expressed BCL6 mRNA equally from the rearranged and the nonrearranged alleles. Neither the nature of the substituted promoters nor the presence of activating mutations in the BCL6 regulatory sequences correlated with the allelic expression of the BCL6 gene in these tumors.

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Acknowledgements

We thank Dr Stephan Gesk for assistance with FISH analysis. This work was supported by grants CA33399 and CA34233 from the USPHS-NIH and grant FIS 01/0015 from Spanish Ministry of Health. RL is an American Cancer Society Clinical Research Professor.

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Authors and Affiliations

  1. Division of Oncology, Department of Medicine, Stanford University Medical Center, Stanford, CA, USA

    I S Lossos, T Akasaka & R Levy

  2. Department of Hematology and Medical Oncology, Hospital Clinico, University of Valencia, Spain

    J A Martinez-Climent

  3. Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany

    R Siebert

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Lossos, I., Akasaka, T., Martinez-Climent, J. et al. The BCL6 gene in B-cell lymphomas with 3q27 translocations is expressed mainly from the rearranged allele irrespective of the partner gene. Leukemia 17, 1390–1397 (2003). https://doi.org/10.1038/sj.leu.2402997

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