Role of early B-cell factor 1 (EBF1) in Hodgkin lymphoma
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 ma...
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Veröffentlicht in: | Leukemia 2013-03, Vol.27 (3), p.671-679 |
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Sprache: | eng |
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Zusammenfassung: | 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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ISSN: | 0887-6924 1476-5551 |
DOI: | 10.1038/leu.2012.280 |