To 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 SamplesTumor-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 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 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.
Transcription factor Runx3 regulates interleukin-15-dependent natural killer cell activation.
Sex, Age, Specimen part
View Samples