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E-MEXP-847
Homo sapiens
14 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
We analyzed mRNAs in transiliacal bone biopsies from 7 patients with primary hyperparathyroidism using Affymetrix HG-U133A Gene Chips Similar analyses of the global transcriptional activity were repeated in a second bone biopsy from the same patient taken one year after surgery and reversal of disease parameters.
Publication Title
Abnormal muscle and hematopoietic gene expression may be important for clinical morbidity in primary hyperparathyroidism.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Subject
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The cellular origin of chronic lymphocytic leukemia (CLL) is debated. Transcriptome analysis of CLL and normal peripheral blood and splenic B cell subsets displayed highest similarity of CLL to mature CD5+ B cells. We identified a distinct CD5+CD27+ post-germinal center B cell subset, and revealed that immunoglobulin V gene mutated CLL are more similar to mutated CD5+ B cells, whereas unmutated CLL are more related to unmutated CD5+ B cells. Stereotyped immunoglobulin V gene rearrangements were significantly enriched among CD5+ B cells, providing further genetic evidence for a derivation of CLL from CD5+ B cells. Moreover, we identified deregulated expression patterns providing novel insights into the pathophysiology of CLL, including downregulation of EBF1 and KLF family members.
Publication Title
Cellular origin and pathophysiology of chronic lymphocytic leukemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 111 Downloadable Samples
- Affymetrix Human Genome U95A Array (hgu95a)
Description
We used high density oligonucleotide arrays to identify molecular correlates of genetically and clinically distinct subgroups of B-cell chronic lymphocytic leukemia (B-CLL). Gene expression profiling was used to profile the five most frequent genomic aberrations, namely deletions affecting chromosome bands 13q14, 11q22-q23, 17p13 and 6q21, and gains of genomic material affecting chromosome band 12q13. A strikingly high degree of correlation between loss or gain of genomic material and the amount of transcripts from the affected regions leads to the hypothesis of gene dosage as a significant pathogenic factor. Furthermore, the influence of the immunoglobulin variable heavy chain (VH) mutation status was determined. A clear distinction in the expression profiles of unmutated and mutated VH samples exists, which can be discovered using unsupervised learning methods. However, when samples were separated by gender, this separation could only be detected in samples from male patients.
Publication Title
Microarray gene expression profiling of B-cell chronic lymphocytic leukemia subgroups defined by genomic aberrations and VH mutation status.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Thalidomide Exerts Distinct Molecular Antileukemic Effects and Combined Thalidomide/Fludarabine Therapy is Clinically Effective in High-Risk Chronic Lymphocytic Leukemia
Publication Title
Thalidomide exerts distinct molecular antileukemic effects and combined thalidomide/fludarabine therapy is clinically effective in high-risk chronic lymphocytic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MYC stimulates EZH2 expression by repression of its negative regulator miR-26a.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Apoptosis is deregulated in most, if not all, cancers, including hematological malignancies. In this study, we wanted to test whether primary acute myeloid leukemia (AML) samples are sensitive for inhibitor of apoptosis (IAP) protein antagonist treatment in vitro, and which AML subgroup might profit most from such a novel therapeutic strategy. We treated diagnostic samples of 67 adult AML patients with either cytarabine (ara-C) or IAP antagonist BV6 and correlated sensitivity with clinical, cytogenetic and molecular markers, and expression levels of selected genes involved in apoptosis. Primary AML samples showed differential sensitivity to treatment with either ara-C (40% sensitive, 17% intermediate, 43% resistant) or BV6 (51% sensitive, 21% intermediate, 28% resistant). Notably, 69% of ara-C resistant samples showed a good to fair response to IAP inhibition. Furthermore, combination treatment of ara-C with BV6 showed additive effects in most samples. Differences in sensitivity to IAP antagonist treatment correlated with significantly elevated expression levels of TNF and lower levels of XIAP in BV6 sensitive samples, as well as with NPM1 mutations. Gene expression profiling pointed to apoptosis-related pathways, which were specifically induced by IAP inhibition in sensitive samples. Thus, our results suggest IAP inhibition as a potential novel therapeutic option in AML.
Publication Title
Targeting inhibitor of apoptosis proteins by Smac mimetic elicits cell death in poor prognostic subgroups of chronic lymphocytic leukemia.
Sample Metadata Fields
Sex, Age, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Inhibitor of apoptosis (IAP) proteins are expressed at high levels in CLL cells and may contribute to evasion of cell death leading to poor therapeutic outcome. Of note, prognostic unfavourable cases with e.g. non-mutated VH-status and TP53 mutation responded significantly better to BV6 than samples with unknown or favourable prognosis e.g. 13q deletion. The majority of cases with 17p deletion (10/12) and Fludarabine refractory cases were sensitive to BV6, indicating that BV6 acts independently of the p53 pathway. Importantly, BV6 dose-dependently induced cell death in 28 of 51 (54%) investigated patient samples while B cells from healthy donors were largely unaffected. BV6 also triggered cell death under survival conditions mimicking the microenvironment e.g. by adding CD40 ligand or in conditioned medium. Gene expression profiling identified cell death- and NF-kB-signaling among the top pathways regulated by BV6. This was confirmed by data showing that BV6 causes degradation of cIAP1 and cIAP2 and NF-kB pathway activation. BV6 induced cell death depended on production of reactive oxygen species, since addition of ROS scavengers significantly rescued BV6-triggerd cell death. In contrast, BV6 induced cell death independently of caspase activity, RIP1 activity or TNF-alpha, since zVAD.fmk, necrostatin-1 or TNF-alpha-blocking antibody Enbrel failed to protect against cell death. Of note, transcripts of ROS regulatory proteins were modulated by BV6. Thus, these data have important implications for developing new therapeutic strategies to overcome cell death resistance in CLL especially in poor prognostic subgroups.
Publication Title
Targeting inhibitor of apoptosis proteins by Smac mimetic elicits cell death in poor prognostic subgroups of chronic lymphocytic leukemia.
Sample Metadata Fields
Sex, Age, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The MYC oncogene, which is commonly mutated/amplified in tumors, represents an important regulator of cell growth owing to its ability to induce both proliferation and apoptosis. Recent evidence links MYC to altered miRNA expression, thereby suggesting that MYC-regulated miRNAs might contribute to tumorigenesis. To further analyze the impact of MYC-regulated miRNAs we investigated a murine lymphoma model harboring the MYC transgene in a Tet-off system in order to control its expression. Microarray-based miRNA expression profiling revealed both known and novel MYC targets. Among the miRNAs repressed by MYC we identified the potential tumor suppressor miR-26a, which possessed the ability to attenuate proliferation in MYC-dependent cells. Interestingly, miR-26a was also found to be deregulated in primary human Burkitt lymphoma samples, thereby likely being of clinical relevance. While today only few miRNA targets have been identified in human disease, we could show that ectopic expression of miR-26a influenced cell cycle progression by targeting the bona fide oncogene EZH2, a Polycomb protein and global regulator of gene expression yet unknown to be regulated by miRNAs. Thus, in addition to directly targeting protein-coding genes, MYC modulates genes important to oncogenesis via deregulation of miRNAs, thereby vitally contributing to MYC-induced lymphomagenesis.
Publication Title
MYC stimulates EZH2 expression by repression of its negative regulator miR-26a.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Krüppel-like factor 4 (KLF4) inactivation in chronic lymphocytic leukemia correlates with promoter DNA-methylation and can be reversed by inhibition of NOTCH signaling.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Whole genome sequencing revealed CLL as a disease of the genome and epigenome defined by somatic mutations and aberrant DNA-methylation. To uncover the impact of aberrant methylation on transcription, gene expression and methylation array profiling was performed in CLL and B-cells. RNA from 13 CLL patients and 6 healthy donor samples was analyzed on expression arrays.
Publication Title
Krüppel-like factor 4 (KLF4) inactivation in chronic lymphocytic leukemia correlates with promoter DNA-methylation and can be reversed by inhibition of NOTCH signaling.
Sample Metadata Fields
Sex
View Samples