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Mus musculus
28 Downloadable Samples
Illumina HiSeq 1500
Description
While recent clinical studies demonstrate the promise of cancer immunotherapy, a barrier for broadening the clinical benefit is identifying how tumors locally suppress cytotoxic immunity. As an emerging mode of intercellular communication, exosomes secreted by malignant cells can deliver a complex payload of coding and non-coding RNA to cells within the tumor microenvironment. Here, we quantified the RNA payload within tumor-derived exosomes and the resulting dynamic transcriptomic response to cytotoxic T cells upon exosome delivery to better understand how tumor-derived exosomes can alter immune cell function. Exosomes derived from B16F0 melanoma cells were enriched for a subset of coding and non-coding RNAs that did not reflect the abundance in the parental cell. Upon exosome delivery, RNAseq revealed the dynamic changes in the transcriptome of CTLL2 cytotoxic T cells. In analyzing transiently co-expressed gene clusters, pathway enrichment suggested that the B16F0 exosomal payload altered mitochondrial respiration, which was confirmed independently, and upregulated genes associated with the Notch signaling pathway. Interestingly, exosomal miRNA appeared to have no systematic effect on downregulating target mRNA levels. Overall design: CTLL2 cells were grown in complete media for 24 hrs, and then stimulated with fresh B16F0 exosomes resuspended in PBS, to a final exosome concentration of 0.2 mg/ml. The transcriptome of untreated CTLL2 cells was assayed at 0, 0.5, 2, 4, and 8 hours after cells were placed in fresh media. There are 4 biological replicates at the 0 hour time point and 3 biological replicates at the 0.5, 2, 4, and 8 hour time points. The transcriptome of CTLL2 cells treated with B16F0 exosomes was assayed at 0.5, 2, 4, and 8 hours after addition of fresh media containing B16F0 exosomes. There were 3 biological replicates performed at each time point.
Publication Title
Exosomes derived from B16F0 melanoma cells alter the transcriptome of cytotoxic T cells that impacts mitochondrial respiration.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 158 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Genome-wide assessment of gene expression in primary acute lymphoblastic leukemia cells was performed to identify genomic determinants of MTXs antileukemic effects. Reduction of circulating leukemia cells after in vivo methotrexate treatment served as a measure MTX's antileukemic effects.
Publication Title
In vivo response to methotrexate forecasts outcome of acute lymphoblastic leukemia and has a distinct gene expression profile.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 129 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Acute lymphoblastic leukemia (ALL) can be cured with combination chemotherapy in over 75% of children, but the cause of treatment failure in the remaining patients is unknown. We determined the sensitivity of ALL cells to individual antileukemic agents in 441 patients, and used a genome-wide approach to identify 45 genes differentially expressed in ALL exhibiting cross-resistance to prednisolone, vincristine, asparaginase and daunorubicin. We also identified a distinct phenotype of discordant resistance to asparaginase and vincristine and 139 genes whose expression was associated with this novel phenotype. The expression of these genes discriminated treatment outcome in two independent patient populations, identifying a subset of patients with a markedly inferior outcome (37%13% 5-year DFS).
Publication Title
Identification of genes associated with chemotherapy crossresistance and treatment response in childhood acute lymphoblastic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 44 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
We identified germline single nucleotide polymorphisms (SNPs) associated with childhood acute lymphoblastic leukemia (ALL) and its subtypes. Using the Affymetrix 500K Mapping array and publicly available genotypes, we identified 18 SNPs whose allele frequency differed (P<1x10-5) between a pediatric ALL population (n=317) and non-ALL controls (n=17,958). Six of these SNPs differed (P0.05) in allele frequency among four ALL subtypes. Two SNPs in ARID5B not only differed between ALL and non-ALL groups (rs10821936, P=1.4x10-15, odds ratio[OR]=1.91; rs10994982, P=5.7x10-9, OR=1.62) but also distinguished B-hyperdiploid ALL from other subtypes (rs10821936, P=1.62 x10-5, OR=2.17; rs10994982, P=0.003, OR 1.72). These ARID5B SNPs also distinguished B-hyperdiploid ALL from other subtypes in an independent validation cohort (n=124 children with ALL) (P=0.003 and P=0.0008, OR 2.45 and 2.86, respectively) and were associated with methotrexate accumulation and gene expression pattern in leukemic lymphoblasts. We conclude that germline genomic variations affect susceptibility to and characteristics of specific ALL subtypes.
Publication Title
Germline genomic variants associated with childhood acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 173 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Cellular drug resistance is associated with an unfavorable prognosis in pediatric acute lymphoblastic leukemia (ALL). To identify genes conferring resistance to antileukemic agents, we analyzed the expression of >12,700 genes in sensitive and resistant ALL cells obtained at diagnosis from 174 patients. This revealed 42, 59, 54 and 22 genes (P0.001) that were differentially expressed in B-lineage ALL that was sensitive versus resistant to prednisolone, vincristine, asparaginase or daunorubicin, respectively, with prediction accuracies of 71-76%. Notably, 149 of the discriminating genes have not been previously associated with resistance to these anticancer agents. These included carbohydrate-metabolism and transcription-associated genes for prednisolone, cytoskeleton and extracellular matrix genes for vincristine, ribosomal protein and translation-associated genes for asparaginase, and RAS signaling and nucleosome remodeling complex genes for daunorubicin. The identification of novel genomic determinants of cellular drug resistance provides new insights for overcoming drug resistance in acute lymphoblastic leukemia.
Publication Title
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 98 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 98 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
There is a distinct signature of differentially expressed probes from diagnosis to relapse
Publication Title
Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies.
Sample Metadata Fields
Specimen part, Disease
View Samples
GSE650- Homo sapiens
- 94 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
primary ALL cells (B- and T-lineage) sensitive to daunorubicinby the MTT in vitro sensitivity assay
Publication Title
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment.
Sample Metadata Fields
No sample metadata fields
View Samples GSE648- Homo sapiens
- 89 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
primary ALL cells (B- and T-lineage) sensitive to vincristine by the MTT in vitro sensitivity assay
Publication Title
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment.
Sample Metadata Fields
No sample metadata fields
View Samples GSE659- Homo sapiens
- 82 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
primary ALL cells (B-lineage) sensitive to daunorubicin by the MTT in vitro sensitivity assay
Publication Title
Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment.
Sample Metadata Fields
No sample metadata fields
View Samples