This SuperSeries is composed of the SubSeries listed below.
Classical Hodgkin's lymphoma shows epigenetic features of abortive plasma cell differentiation.
Specimen part, Cell line, Treatment
View SamplesA 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.
Histone acetylation and DNA demethylation of B cells result in a Hodgkin-like phenotype.
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View SamplesBackground
Classical Hodgkin's lymphoma shows epigenetic features of abortive plasma cell differentiation.
Specimen part, Cell line, Treatment
View SamplesBackground: MYC is a transcription factor encoded by the c-MYC gene (thereafter termed MYC). MYC is key transcription factor involved in many central cellular processes including ribosomal biogenesis. MYC is overexpressed in the majority of human tumours including aggressive B-cell lymphoma especially Burkitt's lymphoma. Although Burkitt's lymphoma is a highlight example for MYC overexpression due to a chromosomal translocation, no global analysis of MYC binding sites by chromatin immunoprecipitation (ChIP) followed by global next generation sequencing (ChIP-Seq) has been conducted so far in Burkitt's lymphoma.
Deep sequencing of MYC DNA-binding sites in Burkitt lymphoma.
Specimen part, Cell line
View SamplesIn the immune system various parameters and immune functions are controlled by the circadian system. To investigate molecular mechanisms that link the circadian clock and the immune system we analyzed the transcriptom of peritoneal macrophages from mice collected in a time course for two consecutive days. We found that more than 8% of expressed genes are under circadian control including many important regulators in pathogen recognition, signal transduction and cytokine secretion.
A circadian clock in macrophages controls inflammatory immune responses.
Sex, Specimen part, Time
View SamplesBackground
Classical Hodgkin's lymphoma shows epigenetic features of abortive plasma cell differentiation.
Specimen part, Cell line
View SamplesBackground
Classical Hodgkin's lymphoma shows epigenetic features of abortive plasma cell differentiation.
Specimen part, Cell line
View SamplesAlternative mRNA splicing represents an effective mechanism of regulating gene function and is a key element to increase the coding capacity of the human genome. Today, an increasing number of reports illustrates that aberrant splicing events are common and functionally important for cancer development. However, more comprehensive analyses are warranted to get novel insights into the biology underlying malignancies like e.g. acute myeloid leukemia (AML). Here, we performed a genome-wide screening of splicing events in AML using an exon microarray platform. We analyzed complex karyotype and core binding factor (CBF) AML cases (n=64) in order to evaluate the ability to detect alternative splicing events distinguishing distinct leukemia subgroups. Testing different commercial and open source software tools to compare the respective AML subgroups, we could identify a large number of potentially alternatively spliced transcripts with a certain overlap of the different approaches. Selected candidates were further investigated by PCR and sequence analysis: out of 24 candidate genes studied, we could confirm alternative splice forms in 8 genes of potential pathogenic relevance, such as PRMT1 regulating transcription through histone methylation and participating in DNA damage response, and PTPN6, which encodes for a negative regulator of cell cycle control and apoptosis. In summary, this first large Exon microarray based study demonstrates that transcriptome splicing analysis in AML is feasible but challenging, in particular with regard to the currently available software solutions. Nevertheless, our results show that alternatively spliced candidate genes can be detected, and we provide a guide how to approach such analyses.
A robust estimation of exon expression to identify alternative spliced genes applied to human tissues and cancer samples.
Specimen part, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
An immediate-late gene expression module decodes ERK signal duration.
Specimen part, Cell line
View SamplesPurpose: In childhood acute lymphoblastic leukemia (ALL), approximately 25% of patients suffer from relapse. In recurrent disease, despite intensified therapy, overall cure rates of 40% remain unsatisfactory and survival rates are particularly poor in certain subgroups. The probability of long-term survival after relapse is predicted from well-established prognostic factors, i. e. time and site of relapse, immunophenotype and minimal residual disease. However, the underlying biological determinants of these prognostic factors remain poorly understood.
No associated publication
Sex
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