Loss of the B-lineage–specific gene expression program in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma

• Ines Schwering

  From the Institute for Genetics and the Department of Internal Medicine I, University of Cologne, Germany; Department of Pathology, University of Frankfurt, Frankfurt/Main, Germany; and the Institute of Cancer Genetics, Columbia University, New York, NY.

• Andreas Bräuninger

  From the Institute for Genetics and the Department of Internal Medicine I, University of Cologne, Germany; Department of Pathology, University of Frankfurt, Frankfurt/Main, Germany; and the Institute of Cancer Genetics, Columbia University, New York, NY.

• Ulf Klein

  From the Institute for Genetics and the Department of Internal Medicine I, University of Cologne, Germany; Department of Pathology, University of Frankfurt, Frankfurt/Main, Germany; and the Institute of Cancer Genetics, Columbia University, New York, NY.

• Berit Jungnickel

  From the Institute for Genetics and the Department of Internal Medicine I, University of Cologne, Germany; Department of Pathology, University of Frankfurt, Frankfurt/Main, Germany; and the Institute of Cancer Genetics, Columbia University, New York, NY.

• Marianne Tinguely

  From the Institute for Genetics and the Department of Internal Medicine I, University of Cologne, Germany; Department of Pathology, University of Frankfurt, Frankfurt/Main, Germany; and the Institute of Cancer Genetics, Columbia University, New York, NY.

• Volker Diehl

  From the Institute for Genetics and the Department of Internal Medicine I, University of Cologne, Germany; Department of Pathology, University of Frankfurt, Frankfurt/Main, Germany; and the Institute of Cancer Genetics, Columbia University, New York, NY.

• Martin-Leo Hansmann

  From the Institute for Genetics and the Department of Internal Medicine I, University of Cologne, Germany; Department of Pathology, University of Frankfurt, Frankfurt/Main, Germany; and the Institute of Cancer Genetics, Columbia University, New York, NY.

• Riccardo Dalla-Favera

  From the Institute for Genetics and the Department of Internal Medicine I, University of Cologne, Germany; Department of Pathology, University of Frankfurt, Frankfurt/Main, Germany; and the Institute of Cancer Genetics, Columbia University, New York, NY.

• Klaus Rajewsky

  From the Institute for Genetics and the Department of Internal Medicine I, University of Cologne, Germany; Department of Pathology, University of Frankfurt, Frankfurt/Main, Germany; and the Institute of Cancer Genetics, Columbia University, New York, NY.

• Ralf Küppers

  From the Institute for Genetics and the Department of Internal Medicine I, University of Cologne, Germany; Department of Pathology, University of Frankfurt, Frankfurt/Main, Germany; and the Institute of Cancer Genetics, Columbia University, New York, NY.

抄録

Hodgkin and Reed-Sternberg (HRS) cells represent the malignant cells in classical Hodgkin lymphoma (HL). Because their immunophenotype cannot be attributed to any normal cell of the hematopoietic lineage, the origin of HRS cells has been controversially discussed, but molecular studies established their derivation from germinal center B cells. In this study, gene expression profiles generated by serial analysis of gene expression (SAGE) and DNA chip microarrays from HL cell lines were compared with those of normal B-cell subsets, focusing here on the expression of B-lineage markers. This analysis revealed decreased mRNA levels for nearly all established B-lineage–specific genes. For 9 of these genes, lack of protein expression was histochemically confirmed. Down-regulation of genes affected multiple components of signaling pathways active in B cells, including B-cell receptor (BCR) signaling. Because several genes down-regulated in HRS cells are positively regulated by the transcriptional activator Pax-5, which is expressed in most HRS cells, we studied HL cell lines for mutations in the Pax-5gene. However, no mutations were found. We propose that the lost B-lineage identity in HRS cells may explain their survival without BCR expression and reflect a fundamental defect in maintaining the B-cell differentiation state in HRS cells, which is likely caused by a novel, yet unknown, pathogenic mechanism.

収録刊行物

• Blood

  Blood 101 (4), 1505-1512, 2003-02-15

  American Society of Hematology

キーワード

• Cell Biology
• Hematology
• Immunology
• Biochemistry

詳細情報

• CRID: 1360574094392253184
• NII論文ID: 30022494605
• DOI: 10.1182/blood-2002-03-0839
• ISSN: 15280020
• ISSN: 00064971
• Web Site: http://ashpublications.org/blood/article-pdf/101/4/1505/1262235/h80403001505.pdf
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