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Classical Hodgkin lymphoma shows epigenetic features of an abortive plasma cellular differentiation: expression of PCM vs. B-cell lines

ABSTRACT: Background Epigenetic changes are involved in the extinction of the B-cell gene expression program of classical Hodgkin lymphoma. However, little is known regarding epigenetic similarities between classical Hodgkin lymphoma and plasma cell myeloma cells, both of which share an extinction of the gene expression program of mature B-cells. Design and methods Global histone H3 acetylation patterns were determined in cell lines derived from classical Hodgkin lymphoma, plasma cell myeloma and B-cell lymphoma by chromatin immunoprecipitation and subsequent hybridization onto promoter tiling arrays. H3K27 trimethylation was analyzed by chromatin immunoprecipitation and real-time DNA-PCR for selected genes. Epigenetic modifications were compared to gene expression data. Results B-cell characteristic genes were hypoacetylated in classical Hodgkin lymphoma and plasma cell myeloma cell lines, as demonstrated by comparison of their histone H3 acetylation patterns to those of B-cell lines. However, the number of genes jointly hyperacetylated and expressed in classical Hodgkin lymphoma and plasma cell myeloma cell lines, such as IFR4/MUM1 and RYBP, is limited. Moreover, H3K27 trimethylation for selected B-cell characteristic genes revealed that this additional epigenetic silencing is much more prevalent in classical Hodgkin lymphoma as compared to plasma cell myeloma. Conclusion Our epigenetic data support the view that classical Hodgkin lymphoma is characterized by an abortive plasma cell differentiation with a down-regulation of B-cell characteristic genes but without activation of most plasma cell typical genes. Gene expression analysis of plasma cell myeloma (PCM) and B-cell lines: Microarray data of the B-cell line Namalwa that was published previously by our group (GEO accession number GSE8388) was analyzed together with newly generated data for the B-cell lines SU-DHL4 and SU-DHL6 (duplicates) and three PCM cell lines (L363, U266, LP1). For all cell lines, RNA was isolated according to standard protocols (Qiagen, Hilden, Germany) and used for Affymetrix GeneChip hybridization (HG-U133A). Microarrays were normalized using RMA, and differential expression was calculated using moderated t-test.

ORGANISM(S): Homo sapiens  

SUBMITTER: Lora Dimitrova   Michael Hummel  Maria Joosten  Karin Zimmermann  Dido Lenze  Volkhard Seitz  Philippe Thomas  Anke Ehlers  Elisabeth Oker  Harald Stein  Ulf Leser  Ulrike Paul  Anke Sommerfeld 

PROVIDER: E-GEOD-28079 | ArrayExpress | 2011-05-05



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