This SuperSeries is composed of the SubSeries listed below.
SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging.
Sex, Age
View SamplesAging is associated with major nuclear changes affecting genomic integrity and gene expression. Here we compare the gene expression profiles in the neocortex of young (5 months old) and old (30 months old) B6xC3 F1 mice.
SIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging.
Sex, Age
View SamplesThis experiment is designed to detect genes differentially expressed in 2uM erlotinib treatment versus DMSO treatment and to identify differential gene set enrichments.
Inhibition of Casein Kinase 1 Alpha Prevents Acquired Drug Resistance to Erlotinib in EGFR-Mutant Non-Small Cell Lung Cancer.
Specimen part, Cell line
View SamplesKnockdown of mutant and/or wild-type SF3B1 in MEL202 cell line by Degron knock-in, followed by RNA-seq, to identify splicing events governed by mutant SF3B1. Overall design: Control: parental MEL202 cell line. Experiments: mutant-SF3B1 knockdown; wildtype-SF3B1 knockdown; mutant SF3B1 knockout. Treatments: each of these four conditions plus and minus shld.
A chemical genetics approach for the functional assessment of novel cancer genes.
No sample metadata fields
View SamplesWe developed a general approach to small molecule library screening called GE-HTS (Gene Expression-Based High Throughput Screening) in which a gene expression signature is used as a surrogate for cellular states and applied it to the identification of compounds inducing the differentiation of acute myeloid leukemia cells. In screening 1,739 compounds, we identified 8 that reliably induced the differentiation signature, and furthermore yielded functional evidence of bona fide differentiation.
Gene expression-based high-throughput screening(GE-HTS) and application to leukemia differentiation.
No sample metadata fields
View SamplesWe developed a general approach to small molecule library screening called GE-HTS (Gene Expression-Based High Throughput Screening) in which a gene expression signature is used as a surrogate for cellular states and applied it to the identification of compounds inducing the differentiation of acute myeloid leukemia cells. In screening 1,739 compounds, we prioritized 15 candidate compounds (2 were already confirmed in the literature). We next evaluated the 13 remaining compounds. Eight reliably induced the differentiation signature, and furthermore yielded functional evidence of bona fide differentiation.
Gene expression-based high-throughput screening(GE-HTS) and application to leukemia differentiation.
No sample metadata fields
View SamplesCure rates for patients with acute myeloid leukemia (AML) remain low despite ever-increasing dose intensity of cytotoxic therapy. In an effort to identify novel approaches to AML therapy, we recently reported a new method of chemical screening based on the modulation of a gene expression signature of interest. We applied this approach to the discovery of AML-differentiation-promoting compounds. Among the compounds inducing neutrophilic differentiation was DAPH1 (4,5-dianilinophthalimide), previously reported to inhibit epidermal growth factor receptor (EGFR) kinase activity. Here we report that the Food and Drug Administration (FDA)-approved EGFR inhibitor gefitinib similarly promotes the differentiation of AML cell lines and primary patient-derived AML blasts in vitro. Gefitinib induced differentiation based on morphologic assessment, nitro-blue tetrazolium reduction, cell-surface markers, genome-wide patterns of gene expression, and inhibition of proliferation at clinically achievable doses. Importantly, EGFR expression was not detected in AML cells, indicating that gefitinib functions through a previously unrecognized EGFR-independent mechanism. These studies indicate that clinical trials testing the efficacy of gefitinib in patients with AML are warranted.
Gefitinib induces myeloid differentiation of acute myeloid leukemia.
Disease, Disease stage, Cell line
View SamplesWe developed a general approach to small molecule library screening called GE-HTS (Gene Expression-Based High Throughput Screening) in which a gene expression signature is used as a surrogate for cellular states and applied it to the identification of compounds inducing the differentiation of acute myeloid leukemia cells. In screening 1,739 compounds, we identified 8 that reliably induced the differentiation signature, and furthermore yielded functional evidence of bona fide differentiation. We tested several of these in duplicate replicates in blasts from a patient with APL. Also included in this data set are a collection of 6 primary patient AML cells, 3 normal neutrophils samples, and 3 normal monocyte samples. This data was used to evaluate whole genome effects of the compounds on APL cells in relation to AML versus normal neutrophils and monocytes.
Gene expression-based high-throughput screening(GE-HTS) and application to leukemia differentiation.
No sample metadata fields
View SamplesThis study compared the expression signatures of HL60 cells +/- tretinoin. This data was then used for another study showing a method for high-throughput gene expression signature analysis.
A method for high-throughput gene expression signature analysis.
No sample metadata fields
View SamplesWe sorted Eomes-negative NK cells (CD3- CD56+ CXCR6- CD16-) and Eomes-positive NK cells (CD3- CD56+ CXCR6+) from total leukocytes isolated from the perfusion fluid of five healthy human livers destined for transplantation. Total RNA was extracted from sorted cells, cDNA generated and RNASeq performed. Overall design: Examination of mRNA levels in paired Eomes-negative/Eomes-positive NK cells from the same donor.
Eomeshi NK Cells in Human Liver Are Long-Lived and Do Not Recirculate but Can Be Replenished from the Circulation.
Specimen part, Subject
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