Abstract
A hallmark of classical Hodgkin lymphoma (cHL) is that the B-cell-derived Hodgkin and Reed–Sternberg (HRS) tumor cells have largely lost the B-cell-typical gene expression program. The factors causing this ‘reprogramming’ of HRS cells are only partly understood. As early B-cell factor 1 (EBF1), a major B-cell transcription factor, is downregulated in HRS cells, we analyzed whether this downregulation contributes to the lost B-cell phenotype and tested the consequences of EBF1 re-expression in cHL cell lines. EBF1 re-expression caused an upregulation of B-cell genes, such as CD19, CD79A and CD79B, although the B-cell genes FOXO1 and PAX5 remained lowly expressed. The re-expression of CD19, CD79A and CD79B occurred largely without demethylation of promoter CpG motifs of these genes. In the cHL cell line L-1236 fitness decreased after EBF1 re-expression. These data show that EBF1 has the ability to reintroduce part of the B-cell signature in cHL cell lines. Loss of EBF1 expression in HRS cells therefore contributes to their lost B-cell phenotype. Notably, in the cHL cell line KM-H2 destructive mutations were found in one allele of EBF1, indicating that genetic lesions may sometimes have a role in impairing EBF1 expression.
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Acknowledgements
We thank Gwen Lorenz for expert technical assistance, Klaus Lennartz for cell sorting and Jens Stanelle for helpful discussions. This work was supported by the Deutsche Krebshilfe (108687).
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Bohle, V., Döring, C., Hansmann, ML. et al. Role of early B-cell factor 1 (EBF1) in Hodgkin lymphoma. Leukemia 27, 671–679 (2013). https://doi.org/10.1038/leu.2012.280
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DOI: https://doi.org/10.1038/leu.2012.280
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