Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Differential gene expression analysis of pediatric acute myeloid leukemia cell lines treated with azacytidine and panobinostat alone or in combination and compared to vehicle treated cells.

ABSTRACT: Pediatric AML cell lines (MV4;11, AML-193 and THP-1) were treated with DNA hypomethylating agent (azacytidine) and a pan histone deactylase inhibitor (panobinostat) alone or in combination. Treatment of AML cell lines with these epigenetic drugs synergistically suppresses cell viability in vitro and in xenograft models in vivo. Data show differential regulation of gene expression in AML cell lines by epigenetic drugs at concentrations which retained cell viability at a minimum of 75% even in the combination treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE83983 | GEO | 2017/07/01

SECONDARY ACCESSION(S): PRJNA327744

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Phosphoproteome Analysis Reveals Differential Mode of Action of Sorafenib in Wildtype and Mutated FLT3 AML Cells

Project description:Constitutively activating internal tandem duplication (ITD) alterations of the receptor tyrosine kinase FLT3 (Fms-like tyrosine kinase 3) are common in acute myeloid leukemia (AML) and classifies FLT3 as an attractive therapeutic target. So far, application of FLT3 small molecule inhibitors such as Sorafenib has resulted only in partial and transient clinical responses in FLT3-ITD+ patients. Only recently, a prolonged event-free survival has been observed in AML patients who were treated with Sorafenib in addition to standard therapy. Here, we studied the Sorafenib effect on proliferation in a panel of 13 FLT3-ITD- and FLT3-ITD+ AML cell lines. Sorafenib IC50 values ranged from 0.001 to 5.6 µM, whereas FLT3-ITD+ cells (MOLM-13, MV4;11) were found more sensitive to Sorafenib than FLT3-ITD- cells. However, we identified two FLT3-ITD- cell lines (MONO-MAC-1 and OCI-AML-2) which were also Sorafenib sensitive. Phosphoproteome analyses revealed that the affected pathways differed in Sorafenib sensitive FLT3-ITD- and FLT3-ITD+ cells. In MV4;11 cells Sorafenib suppressed mTOR signalling by inhibiting direct inhibition of FLT3. In MONO-MAC-1 cells Sorafenib inhibited the MEK/ERK pathway by inhibition of the RET tyrosine kinase. These data suggest that the FLT3 status in AML patients might not be the only predictive factor for a response to Sorafenib.

2017-05-02 | PXD004442 | Pride

IKAROS and MENIN are Functionally Cooperative Therapeutic Targets in Acute Myeloid Leukemia [RNA-seq]

Project description:Using RNA-seq we examined the transcriptional changes following IKAROS degradation, MENIN-inhibition or the drug combination in the MOLM13 and MV4;11 human MLL-fusion acute myeloid leukemia cell lines and the CBAM-68552 patient-derived xenograft model.

2022-03-10 | GSE168462 | GEO

Multi-omics of azacitidine-treated AML cells reveals variable and convergent targets that remodel the cell surface proteome

Project description:Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are diseases of abnormal hematopoietic differentiation with aberrant epigenetic alterations. Azacitidine (AZA) is a DNA methyltransferase inhibitor (DNMTi) widely used to treat MDS and AML, yet the impact of AZA on the cell surface proteome has not been defined. To identify potential therapeutic targets for use in combination with AZA in AML patients, we investigated the effects of AZA treatment on four AML cell lines representing different stages of differentiation. The effect of AZA treatment on these cell lines was characterized at three levels: the DNA methylome, the transcriptome, and the cell surface proteome. Untreated AML cell lines showed substantial overlap at all three omics level; however, while AZA treatment globally reduced DNA methylation in all cell lines, changes in the transcriptome and surface proteome were subtle and differed among the cell lines. Transcriptome analysis identified five commonly up-regulated coding genes upon AZA treatment in all four cell lines, TRPM4 being the only gene encoding a surface protein, and surface proteomics analysis found no commonly regulated proteins. Gene Set Enrichment Analysis (GSEA) of differentially-regulated RNA and surface proteins showed a decrease in metabolism pathways and an increase in immune defense response pathways. As such, AZA treatment led to diverse effects at the individual gene and protein level but converged to common responses at the pathway level. Given the heterogeneous responses in the four cell lines, we discuss potential therapeutic strategies for AML in combinations with AZA.

2018-10-07 | MSV000083006 | MassIVE

Gene expression profile of human leukemic cell line with cMyc mutations

Project description:RNA-sequencing revealed that c-Myc-related gene signatures were negatively enriched in MV4;11(K148R) cells as compared to parental MV4;11, suggesting that lack of acetylation at K148 results in diminished c-Myc activity. In contrast, MV4;11(K148Q) cells exhibit a positive enrichment of c-Myc-regulated gene signatures as compared to MV4;11(K148R) cells, confirming that loss of acetylation of c-Myc at K148 results in diminished transcriptional activity in AML cells

2023-10-01 | GSE185295 | GEO

MicroRNA in combination with HER2-targeting drugs reduces breast cancer cell viability in vitro

Project description:MicroRNA in combination with HER2-targeting drugs reduces breast cancer cell viability in vitro

| PRJNA686377 | ENA

Transcriptional profiling of LS1034 cells treated with tepoxalin

Project description:LS1034 colorectal cancer cells were treated with DMSO vehicle control or 12 uM tepoxalin for 6 hours. Anti-cancer uses of non-oncology drugs have been found on occasion, but such discoveries have been serendipitous and rare. To fully discover activity against multiple tumor types, resource-intensive screening across hundreds of cancer cell lines is needed. We sought to create a public resource containing the growth inhibitory activity of 4,518 drugs tested across 578 human cancer cell lines. To accomplish this, we used PRISM, which involves the molecular barcoding of each cell line, followed by pooling of the barcoded lines. Relative barcode abundance following drug treatment versus controls thus reflects cell viability following drug treatment. We found that an unexpectedly large number of non-oncology drugs selectively inhibited subsets of cancer cell lines. Moreover, the killing activity of the majority of these drugs was predictable based on the molecular features of the cell lines. Mechanistic follow-up of several of these compounds revealed novel mechanisms. These results illustrate the potential of the PRISM drug repurposing resource as a starting point for new oncology therapeutic development.

2019-08-08 | GSE133286 | GEO

Gene expression changes in SHI-1 cells following exposure to disulfiram/copper, niclosamde or combined drugs

Project description:Disulfiram and niclosamide were identified as drugs that induced depletion of an MLL-AF9-luciferase fusion protein in THP-1 AML cells, in a bioluminescence sreen. MLL-fusion protein depletion was confirmed in AML and ALL cell lines expressing different MLL-fusion proteins. Combination of disulfiram with niclosamide was found to enhance depletion of MLL-fusion proteins. To investigate whether this enhanced depletion resulted in increased suppression of downstream target genes. MLL-AF6 expressing SHI-1 cells were exposed to disulfiram/copper, nciclosamide or combined drugs. SHI-1 cells were treated for 16 hours with 0.3uM disulfiram / 1uM copper, 5uM niclosamide or combined drugs and RNAseq performed on isolated RNA.

2024-07-03 | GSE262673 | GEO

Gene expression profiles of MV-4-11 AML cells treated HDAC1/2 -selective inhibitor and Azacitidine

Project description:Determine the differences in gene expression profiles of MV-4-11 AML cells treated with HDAC1/2-selective inhibition, azacitidine, or the combination of the two agents. Acute myeloid leukemia (AML) is a heterogeneous group of hematopoietic stem cell disorders characterized by defects in myeloid differentiation and increased proliferation of neoplastic hematopoietic precursor cells. Outcomes for patients with AML remain poor, highlighting the need for novel treatment options. Aberrant epigenetic regulation plays an important role in the pathogenesis of AML, and inhibitors of DNA methyltransferase or histone deacetylase (HDAC) enzymes have exhibited activity in preclinical AML models. Combination studies with HDAC inhibitors plus DNA methyltransferase inhibitors have suggested beneficial clinical activity in AML, however the toxicity profiles of non-selective HDAC inhibitors in the combination setting limit their clinical utility. In this work, we describe the preclinical development of selective inhibitors of HDAC1 and HDAC2, which are hypothesized to have improved safety profiles, for combination therapy in AML. We demonstrate that selective inhibition of HDAC1 and HDAC2 is sufficient to achieve efficacy both as a single agent and in combination with azacitidine in preclinical models of AML, including established AML cell lines, leukemia cells from AML patient bone marrow samples and in vivo xenograft models of human AML. Gene expression profiling of AML cells treated with either an HDAC1/2 inhibitor, azacitidine, or the combination of both have identified a list of genes involved in transcription and cell cycle regulation as potential mediators of the combinatorial effects of HDAC1/2 inhibition with azacitidine. Together, these findings support the clinical evaluation of selective HDAC1/2 inhibitors in combination with azacitidine in AML patients.

2017-03-08 | GSE84440 | GEO

RNA-seq of human MDS/AML cell line OCI-M2 treated with 5-azacytidine and sulforaphane

Project description:The RNA sequencing experiment is part of the study: “Modulating Redox Balance Restores Azacytidine Efficacy in Hypomethylating Agent Resistant Disease.” In the study we generated myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) OCI-M2 cell line that is resistant to hypomethylating therapy by 5-azacytidine (AZA). By modulation of the redox environment via modification of redox sensor KEAP1 using sulforaphane (SFN) in these cells we were able to restore sensitivity to AZA. We used RNA sequencing to define transcriptomic differences between AZA sensitive (AZA-S) and AZA resistant (AZA-R) cells and to characterize how the transcriptome is changing upon treatment of these cells with AZA, SFN and combination of both.

2021-07-16 | E-MTAB-10635 | biostudies-arrayexpress

Metabolomics Workbench ST000288 - GNPS - Metabolomic profiling of AML Cell Lines

Project description:In vitro study with AML cell lines that are treated with different concentrations of cytarabine (nucleoside analog). 8 AML cell lines were incubated for 24hr with 0uM, 1uM and 10uM ara-C. After 24hr the cells were washed and pellets were stored in -80°C for genomic and metabolomic analysis.

2018-08-02 | MSV000082685 | GNPS

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data