Item type:Thesis, Open Access

Regulationsmechanismen des Interferon regulatorischen Faktors IRF-4 in der chronisch myeloischen Leukämie

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Date

2005-09-26

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Philipps-Universität Marburg
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Abstract

There is mounting evidence that the deregulation a family of transcription factors, the interferon regulatory factors (IRFs),is implicated in the pathogenesis of CML. The expression of the interferon regulatory factor IRF-4 is downregulated in T cells of CML patients in chronic phase and its increase is associated with a good response to therapy with interferon alpha. Promoter methylation of CpG target sites or direct deletions/insertions of genes are mechanisms of a reversible or permanent deregulation of gene expression, respectively. Therefore, it was examined whether methylation or mutation of the IRF-4 promotor may be involved in the regulation of IRF-4 expression in leukemia cell lines. Whereas promoter mutations or structural rearrangements could be excluded as a cause of altered IRF-4 expression in hematopoietic cells, the IRF-4 promoter methylation status was found to significantly influence IRF-4 transcription. Treatment of IRF-4-negative lymphoid, myeloid and monocytic cell lines with the methylation-inhibitor 5-aza-2-deoxycytidine resulted in a time- and concentration-dependent increase of IRF-4 mRNA and protein levels. Using a restriction-PCR-assay and bisulfit-sequencing we identified specifically methylated CpG sites in IRF-4-negative but not in IRF-4-positive cells. An association of methylational status and mRNA expression of DNA methyltransferases (DNMT) or methyl-CpG-binding proteins (MBP)was not detected. Together, these data suggest CpG site-specific IRF-4 promoter methylation as a putative mechanism of deregulated IRF-4 expression in leukemia.

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Dates
Created: 2005Issued: 2005-09-26Updated: 2011-08-10
DOI
https://doi.org/10.17192/z2005.0418
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
Interferon regulatorischer FaktorIRF-4InterferonChronic myeloid leukemiaDNA methylation5-Aza-2-deoxycytidin ,IRF-4Epigenetik
DFG-subjects
Chronisch-myeloische LeukämiePromotor InterferonMethylierung
DDC-Numbers
610
License
https://rightsstatements.org/vocab/InC-NC/1.0/
URI
https://open.uni-marburg.de/handle/10.17192/z2005.0418
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Ortmann, Christina (130385786): Regulationsmechanismen des Interferon regulatorischen Faktors IRF-4 in der chronisch myeloischen Leukämie. : Philipps-Universität Marburg 2005-09-26. DOI: https://doi.org/10.17192/z2005.0418.

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