Nature Immunology 7, 207 - 215 (2005)
Published online: 20 December 2005; Corrected online: 04 January 2006 | doi:10.1038/ni1285
Intrinsic inhibition of transcription factor E2A by HLH proteins ABF-1 and Id2 mediates reprogramming of neoplastic B cells in Hodgkin lymphomaStephan Mathas1, 2, 5, Martin Janz1, 2, 5, Franziska Hummel2, Michael Hummel3, Brigitte Wollert-Wulf2, Simone Lusatis2, Ioannis Anagnostopoulos3, Andreas Lietz2, Mikael Sigvardsson4, Franziska Jundt1, 2, Korinna Jöhrens3, Kurt Bommert2, Harald Stein3
& Bernd Dörken1, 21
Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany. 2
Hematology, Oncology and Tumorimmunology, Charité, Medical University Berlin, Campus Virchow-Klinikum, Campus Berlin-Buch, 13353 Berlin, Germany. 3
Institute for Pathology, Charité, Medical University Berlin, Campus Benjamin Franklin, 12200 Berlin, Germany. 4
Department for Hematopoietic Stemcell Biology, Stemcell Center, Lund University, S221 84 Lund, Sweden. 5
These authors contributed equally to this work.
Correspondence should be addressed to Stephan Mathas smathas@mdc-berlin.de B cell differentiation is controlled by a complex network of lineage-restricted transcription factors. How perturbations to this network alter B cell fate remains poorly understood. Here we show that classical Hodgkin lymphoma tumor cells, which originate from mature B cells, have lost the B cell phenotype as a result of aberrant expression of transcriptional regulators. The B cell–specific transcription factor program was disrupted by overexpression of the helix-loop-helix proteins ABF-1 and Id2. Both factors antagonized the function of the B cell–determining transcription factor E2A. As a result, expression of genes specific to B cells was lost and expression of genes not normally associated with the B lineage was upregulated. These data demonstrate the plasticity of mature human lymphoid cells and offer an explanation for the unique classical Hodgkin lymphoma phenotype.
* NOTE: In the version of this article initially published online, the directions to the panels for Figure 6e were incorrect in the legend and text. The legend for this panel should begin as follows: "Immunoblot (top), EMSA (bottom left) and RT-PCR (bottom right)...." The accompanying text should read as follows: "Transfection of L428 cells with a combination of these siRNAs efficiently reduced ABF-1 protein expression (Fig. 6e, top) and resulted in a substantial loss of E2A–ABF-1 DNA-binding activity (Fig. 6e, bottom left). After reduction of ABF-1 expression, we noted considerable downregulation of CSF1R and TCF7 expression and a moderate suppression of GATA3 expression (Fig. 6e, bottom right)." The error has been corrected for the HTML and print versions of the article.
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