Role of early B-cell factor 1 (EBF1) in Hodgkin lymphoma.
Leukemia, 2013/3;27(3):671-9.
Bohle V[1], Döring C, Hansmann ML, Küppers R
Affiliations
PMID: 23174882DOI: 10.1038/leu.2012.280
Impact factor: 12.883
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.
MeSH terms
Apoptosis; B-Lymphocytes; Base Sequence; Biomarkers, Tumor; Blotting, Western; Cell Proliferation; CpG Islands; DNA Methylation; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Hodgkin Disease; Humans; Molecular Sequence Data; Oligonucleotide Array Sequence Analysis; Promoter Regions, Genetic; RNA, Messenger; Real-Time Polymerase Chain Reaction; Reed-Sternberg Cells; Reverse Transcriptase Polymerase Chain Reaction; Sequence Homology, Nucleic Acid; Trans-Activators
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