Background: Gene expression profiling has shown its ability to identify with high accuracy low cytogenetic risk acute myeloid leukemia such as acute promyelocytic leukemia and leukemias with t(8;21) or inv(16). The aim of this gene expression profiling study was to evaluate to what extent suboptimal samples with low leukemic blast load (range, 2-59%) and/or poor quality control criteria could also be correctly identified. Methods: Specific signatures were first defined so that all 71 acute promyelocytic leukemia, leukemia with t(8;21) or inv(16)-AML as well as cytogenetically normal acute myeloid leukemia samples with at least 60% blasts and good quality control criteria were correctly classified (training set). The classifiers were then evaluated for their ability to assign to the expected class 111 samples considered as suboptimal because of a low leukemic blast load (n=101) and/or poor quality control criteria (n=10) (test set). Results: With 10-marker classifiers, all training set samples as well as 97 of the 101 test samples with a low blast load, and all 10 samples with poor quality control criteria were correctly classified. Regarding test set samples, the overall error rate of the class prediction was below 4 percent, even though the leukemic blast load was as low as 2%. Sensitivity, specificity, negative and positive predictive values of the class assignments ranged from 91% to 100%. Of note, for acute promyelocytic leukemia and leukemias with t(8;21) or inv(16), the confidence level of the class assignment was influenced by the leukemic blast load. Conclusion: Gene expression profiling and a supervised method requiring 10-marker classifiers enable the identification of favorable cytogenetic risk acute myeloid leukemia even when samples contain low leukemic blast loads or display poor quality control criterion.
Routine use of microarray-based gene expression profiling to identify patients with low cytogenetic risk acute myeloid leukemia: accurate results can be obtained even with suboptimal samples.
Time
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Routine use of microarray-based gene expression profiling to identify patients with low cytogenetic risk acute myeloid leukemia: accurate results can be obtained even with suboptimal samples.
Specimen part, Time
View SamplesThe cellular origin of Ewing tumor (ET), a tumor of bone or soft tissues characterized by specific fusions between EWS and ETS genes, is highly debated. Through gene expression analysis comparing ETs with a variety of normal tissues, we show that the profiles of different EWS-FLI1-silenced Ewing cell lines converge toward that of mesenchymal stem cells (MSC). Moreover, upon EWS-FLI1 silencing, two different Ewing cell lines can differentiate along the adipogenic lineage when incubated in appropriate differentiation cocktails. In addition, Ewing cells can also differentiate along the osteogenic lineage upon long-term inhibition of EWS-FLI1. These in silico and experimental data strongly suggest that the inhibition of EWS-FLI1 may allow Ewing cells to recover the phenotype of their MSC progenitor.
Mesenchymal stem cell features of Ewing tumors.
Specimen part
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Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle.
Specimen part, Treatment
View SamplesBackground: Cancer cachexia is a life-threatening metabolic syndrome that causes significant loss of skeletal muscle mass and significantly increases mortality in cancer patients. Currently, there is an urgent need for better understanding of the molecular pathophysiology of this disease, so that effective therapies can be developed. Almost all pre-clinical studies evaluating skeletal muscle’s response to cancer have focused on one or two pre-clinical models, and almost all have focused specifically on limb muscles. In the current study, we reveal key differences in the histology and transcriptomic signatures of a limb muscle and a respiratory muscle in orthotopic pancreatic cancer patient-derived xenograft (PDX) mice. Methods: To create the four cohorts of PDX mice evaluated in this study, tumors resected from four pancreatic ductal adenocarcinoma (PDAC) patients were portioned and attached to the pancreas of immunodeficient NSG mice. Results: Body weight, muscle mass, and fat mass were significantly decreased in each PDX line. Histological assessment of cryosections taken from the tibialis anterior (TA) and diaphragm (DIA) revealed differential effects of tumor-burden on their morphology. Subsequent genome-wide microarray analysis on TA and DIA revealed key differences between their transcriptomes in response to cancer as well. Indeed, upregulated genes in the diaphragm were enriched for extracellular matrix (ECM) protein-encoding genes and genes related to the inflammatory response, and downregulated genes were enriched for mitochondria related protein-encoding genes. Conversely, the TA showed upregulation of canonical atrophy-associated pathways such as ubiquitin-mediated protein degradation and apoptosis and enrichment of downregulated genes encoding ECM proteins. Conclusions: These data suggest that distinct biological processes account for wasting in different skeletal muscles in response to the same tumor burden. Further investigation into these differences will be critical for the future development of effective clinical strategies to counter cancer cachexia.
Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle.
Specimen part, Treatment
View SamplesWe demonstrate that Prnp dosage is critical for the maintenance of neuronal homeostasis since both its absence and, more relevantly, its overexpression induce higher sensitivity to kainate (KA) damage. These data correlate with electrophysiological results in freely behaving mutant mice showing an imbalance in activity-dependent synaptic processes, as determined from input/output curves, paired-pulse facilitation, and LTP studies. Gene expression profiling showed that 129 genes involved in canonical pathways such as Ubiquitination or Neurotransmission among others were co-regulated in knockout and PrPc overexpressing mice. RT-qPCR analysis of neurotransmission-related genes confirmed GABA-A and AMPA-Kainate receptor subunit transcriptional co-regulation in both Prnp -/- and Tg20 mice. Our results demonstrate that PrPc is necessary for the proper homeostatic functioning of hippocampal circuits, because of its interactions with GABAA and AMPA-Kainate receptors.
Regulation of GABA(A) and glutamate receptor expression, synaptic facilitation and long-term potentiation in the hippocampus of prion mutant mice.
Sex
View SamplesSerum levels of interleukin-8 (IL-8) are increased in the serum of people with pancreatic cancer and associated with the loss of body weight and low muscle mass. We have identified that systemic (intraperitoneal) injection of IL-8 into mice induces significant skeletal muscle atrophy. Transcriptional profiling of muscle harvested from these same mice identified the genes and biological processes associated with this IL-8 induced atrophy including gene clusters related to chromatin modification, muscle cell differentiation, and ubiquitin ligase complex.
IL-8 Released from Human Pancreatic Cancer and Tumor-Associated Stromal Cells Signals through a CXCR2-ERK1/2 Axis to Induce Muscle Atrophy.
Treatment
View SamplesCharacterization of different astrocytes soruces was done using RNAseq including samples from human primary adult brain, astrocytoma, and hiPSC derived astrocytes including neural stem cell origin Overall design: Full RNAseq (>200nt) of biological triplicates isolated with Illumina TrueSeq Stranded mRNA LT Sample Prep Kit and sequenced using Illumina NextSeq 500 sequencer
Human iPS-Derived Astroglia from a Stable Neural Precursor State Show Improved Functionality Compared with Conventional Astrocytic Models.
Specimen part, Subject
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Genome-wide profiling of methylation identifies novel targets with aberrant hypermethylation and reduced expression in low-risk myelodysplastic syndromes.
Specimen part
View SamplesGenome-wide expression and methylation profiling identifies novel targets with aberrant hypermethylation and reduced expression in low-risk myelodysplastic syndromes (MDSs).
Genome-wide profiling of methylation identifies novel targets with aberrant hypermethylation and reduced expression in low-risk myelodysplastic syndromes.
Specimen part
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