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| Status |
Public on Nov 01, 2007 |
| Title |
Epigenetic upregulation of B-cell inappropriate genes induces extinction of B-cell program in classical Hodgkin lymphoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
A unique feature of the tumour cells (Hodgkin/Reed-Sternberg (HRS)) of classical Hodgkin lymphoma (cHL) is the loss of their B-cell phenotype despite their B-cell origin. Several lines of evidence suggest that epigenomic events, especially promoter DNA-methylation, are involved in this silencing of many B-cell associated genes. Here we show that DNA-demethylation alone or in conjunction with histone-acetylation is not able to reconstitute the B-cell gene expression program in cultured HRS cells. Instead, combined DNA-demethylation and histone-acetylation of B cells induce a nearly complete extinction of their B-cell expression program and a tremendous up-regulation of numerous cHL characteristic genes including key players such as Id2 known to be involved in the suppression of the B-cell phenotype. Since the up-regulation of cHL characteristic genes and the extinction of the B-cell expression program occurred simultaneously, epigenetic changes may also be responsible for the malignant transformation of cHL. The epigenetic up-regulation of cHL characteristic genes thus play - in addition to promoter DNA-hypermethylation of B-cell associated genes – a pivotal role for the reprogramming of HRS cells and explain why DNA-demethylation alone is unable to reconstitute the B-cell expression program in HRS cells.
Keywords: Epigenetic modification
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| Overall design |
5-aza-dC treatment:
The cHL derived cell lines L428, KMH2 and L1236 were treated with 5-aza-dC at a concentration of 5 µM for 5 days with drug and medium replacement after each 48 hours.
Combined 5-aza-dC/TSA treatment:
The Burkitt lymphoma derived cell lines (Daudi, Namalwa and Raji)were treated with 5-aza-dC at a concentration of 3 µM for 6 days. 5-aza-dC and medium was replaced at day 2 and 5. At the fifth day - in addition to 3 µM 5-aza-dC - cells were incubated for 24 hours with 625 nM TSA.
The gene expression profiles of the untreated and treated cell lines were generated in duplicates.
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| Contributor(s) |
Ehlers A, Oker E, Bentink S, Lenze D, Stein H, Hummel M |
| Citation(s) |
18256685 |
| |
| Submission date |
Jul 05, 2007 |
| Last update date |
Aug 10, 2018 |
| Contact name |
Anke Ehlers |
| E-mail(s) |
[email protected]
|
| Organization name |
Charité Universitätsmedizin
|
| Department |
Institute of Pathology
|
| Street address |
Hindenburgdamm 30
|
| City |
Berlin |
| State/province |
Berlin |
| ZIP/Postal code |
12200 |
| Country |
Germany |
| |
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| Platforms (1) |
| GPL96 |
[HG-U133A] Affymetrix Human Genome U133A Array |
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| Samples (24)
|
| GSM207568 |
Daudi + 5 µM 5-aza-dC (6 days) + 625 nM TSA (24 h) (1) |
| GSM207577 |
Daudi + 5 µM 5-aza-dC (6 days) + 625 nM TSA (24 h) (2) |
| GSM207578 |
Daudi untreated (1) |
|
| Relations |
| BioProject |
PRJNA101427 |
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