Tumor-associated blood vessels differ from normal vessels at the morphological and molecular level. Proteins that are only present on tumor vessels may serve as biomarkers and as therapeutic targets for inhibition of angiogenesis in cancer. Comparing the transcriptional profiles of blood vascular endothelium from human invasive bladder cancer and from normal bladder tissue, we found several markers that could serve as novel biomarkers or therapeutic targets.
Endocan is upregulated on tumor vessels in invasive bladder cancer where it mediates VEGF-A-induced angiogenesis.
Sex, Disease stage
View SamplesTo elucidate the gene expression footprint of antigenically challenged T-cells which had been treated with anti-LFA-1, CTLA4Ig, anti-CD40-ligand antibodies, we performed microarray gene expression analysis comparing the expression profile of costimulatory blockade treated and untreated responder T-cells.
Short-term immunosuppression promotes engraftment of embryonic and induced pluripotent stem cells.
Specimen part
View SamplesChromosomal rearrangements involving the mixed-lineage leukemia (MLL) gene occur in primary and treatment-related leukemias, and confer a poor prognosis. Studies based primarily on mouse models have substantially advanced our understanding of MLL leukemia pathogenesis, but often employ supra-physiologic oncogene expression with uncertain implications for human leukemia. Genome editing using site-specific nucleases provides a powerful new technology for gene modification to potentially model human disease, however this approach has not been used to recreate acute leukemia in human cells of origin comparable to disease observed in patients. We applied TALEN-mediated genome editing to generate endogenous MLL-AF9 and MLL-ENL oncogenes through insertional mutagenesis in primary human hematopoietic stem and progenitor cells (HSPCs) derived from human umbilical cord blood. Engineered HSPCs displayed altered in vitro growth potentials and induced acute leukemias following transplantation in immuno-compromised mice at a mean latency of 14.5 weeks. The leukemias displayed phenotypic and morphologic similarities with patient leukemia blasts including a subset with mixed phenotype, a distinctive feature seen in clinical disease. The leukemic blasts expressed an MLL-associated transcriptional program with elevated levels of crucial MLL target genes, displayed heightened sensitivity to DOT1L inhibition, and demonstrated increased oncogenic potential ex vivo and in secondary transplant assays. Thus, genome editing to create endogenous MLL oncogenes in primary human HSPCs faithfully models acute MLL-rearranged leukemia and provides an experimental platform for prospective studies of leukemia initiation and stem cell biology in a genetic subtype of poor prognosis leukemia.
MLL leukemia induction by genome editing of human CD34+ hematopoietic cells.
Specimen part
View SamplesSmall nucleolar RNAs (snoRNAs) and small Cajal body-specific RNAs are non-coding RNAs involved in the maturation of other RNA molecules. Alterations of sno/scaRNA expression may play a role in cancerogenesis. This study elucidates the patterns of sno/scaRNA expression in highly purified cells from 211 chronic lymphocytic leukemia (CLL) patients (Binet stage A) also in comparison with those of different normal B-cell subsets. CLLs display a sno/scaRNAs expression profile similar to normal memory, nave and marginal-zone B-cells, with the exception of a few down-regulated transcripts (SNORA31, -6, -62, and -71C). Our analyses also suggest some heterogeneity in the pattern of sno/scaRNAs expression which is apparently unrelated to the major biological (ZAP-70 and CD38), molecular (IGHV mutation) and cytogenetic markers. Moreover, we found that SNORA70F was significantly down-regulated in poor prognostic subgroups and this phenomenon was associated with the down-regulation of its host gene COBLL1. Finally, we generated an independent model based on SNORA74A and SNORD116-18 expression, which appears to distinguish two different prognostic CLL groups. These data extend the view of sno/scaRNAs deregulation in cancer and may contribute to discover novel biomarkers associated with the disease and potentially useful to predict the clinical outcome of early stage CLL patients.
Small nucleolar RNAs as new biomarkers in chronic lymphocytic leukemia.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Runx3-mediated transcriptional program in cytotoxic lymphocytes.
Sex, Age, Specimen part, Treatment
View SamplesNK cells are innate immune cells that recognize and kill foreign, virally-infected and tumor cells without the need for prior immunization. NK expansion following viral infection is IL-2 or IL-15-dependent.
Runx3-mediated transcriptional program in cytotoxic lymphocytes.
Sex, Age, Specimen part, Treatment
View SamplesNK cells are innate immune cells that recognize and kill foreign, virally-infected and tumor cells without the need for prior immunization. NK expansion following viral infection is IL-2 or IL-15-dependent.
Runx3-mediated transcriptional program in cytotoxic lymphocytes.
Sex, Age, Specimen part
View SamplesCD8+T cells are immune cells that recognize foreign antigens on infected and tumor cells, leading to cytokine-dependent expansion and activation of cytotoxicity towards the targets.
Runx3-mediated transcriptional program in cytotoxic lymphocytes.
Sex, Age, Specimen part
View SamplesCD8+T cells are immune cells that recognize foreign antigens on infected and tumor cells, leading to cytokine-dependent expansion and activation of cytotoxicity towards the targets.
Runx3-mediated transcriptional program in cytotoxic lymphocytes.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcription factor Runx3 regulates interleukin-15-dependent natural killer cell activation.
Sex, Age, Specimen part
View Samples