title: Role of early B-cell factor 1 (EBF1) in Hodgkin lymphoma.
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.
authors.affiliation: University of Duisburg-Essen, Medical School, Essen, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Bohle
authors.forename: C
authors.initials: C
authors.lastname: Döring
authors.forename: M-L
authors.initials: ML
authors.lastname: Hansmann
authors.forename: R
authors.initials: R
authors.lastname: Küppers
mesh_terms: D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation; D018899:CpG Islands; D019175:DNA Methylation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D016539:Reed-Sternberg Cells / Q000378:metabolism / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C081976:EBF1 protein, human; D012333:RNA, Messenger; D015534:Trans-Activators