Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Inhibition of pyrimidine biosynthesis targets protein translation in AML [RNA-seq_MN]

ABSTRACT: Investigation of the transcriptional profile of MLL-rearranged AML in response to DHODH inhibition by AG636. Chemo-refractory syngeneic murine AML model driven by doxycycline-inducible expression of MLL-AF9 and constitutive expression of oncogenic Nras (MN) was transplanted into Ptprca recipients. Mice bearing MN tumors were treated with doxycycline or AG636 for one or four days. Leukemic stem cells (cKit high; CD11b low) from bone marrow and spleen were isolated and RNA sequencing performed.

ORGANISM(S): Mus musculus

PROVIDER: GSE181661 | GEO | 2022/04/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Inhibition of pyrimidine biosynthesis targets protein translation in AML [Targeted_CRISPR_screen]

Project description:Investigating genes that increase or decrease treatment efficacy of AG636 in MLL-AF9; KrasG12D (MN) AML cells.

2022-04-26 | GSE181665 | GEO

Inhibition of pyrimidine biosynthesis targets protein translation in AML [RNA-seq_RUNX1]

Project description:Investigation of the transcriptional profile of AML in response to DHODH inhibition by AG636. RUNX1-RUNX1T1 cells were transplanted into Ptprca recipients. Mice bearing tumors were treated with AG636 for one day. Leukemic stem cells (cKit high; CD11b low) from bone marrow and spleen were isolated and RNA sequencing performed.

2022-04-26 | GSE181664 | GEO

Inhibition of pyrimidine biosynthesis targets protein translation in AML [RNA-seq_I1DN]

Project description:Investigation of the transcriptional profile of AML in response to DHODH inhibition by AG636. I1DN model was generated by co-transduction of foetal liver derived HSPCs with constructs encoding IDH1R132H, DNMT3AR882H and NrasG12D. Cells were transplanted into Ptprca recipients. Mice bearing I1DN tumors were treated with AG636 for one day. Leukemic stem cells (cKit high; CD11b low) from bone marrow and spleen were isolated and RNA sequencing performed.

2022-04-26 | GSE181663 | GEO

Inhibition of pyrimidine biosynthesis targets protein translation in AML [ATAC-seq_MN-2]

Project description:Investigation of the chromatin accessibility in MN cells. Mice bearing MN tumors were treated with AG636 for 2 days. Leukemic stem cells (cKit high; CD11b low) from bone marrow and spleen were isolated. RNA sequencing and ATAC-seq were performed.

2022-04-26 | GSE181660 | GEO

Inhibition of pyrimidine biosynthesis targets protein translation in AML [RNA-seq_MN-2]

Project description:Investigation of the transcriptional profile and compared with the genome accessibility (using ATAC-seq) in MN cells. Mice bearing MN tumors were treated with AG636 for 2 days. Leukemic stem cells (cKit high; CD11b low) from bone marrow and spleen were isolated. RNA sequencing and ATAC-seq were performed.

2022-04-26 | GSE181662 | GEO

RNA sequencing expression analysis of murine MLL-AF9;NRAS acute myeloid leukemia cells silenced for E2-2.

Project description:We investigated the role of the transcriptional regulators Id2 and E2-2 (encoded by Tcf4) in the context of MLL-rearranged acute myeloid leukemia (AML). Using an AML mouse model driven by a Tet-off inducible MLL-AF9 allele co-expressed with oncogenic NRASG12D, we demonstrated that MLL-AF9 regulates the E protein pathway by suppressing Id2, while activating the expression of its target E2-2. Moreover, we found that Id2 over-expression in MLL-AF9 AML cells results inhibition of leukemia growth, loss of leukemia stem cell-associated gene expression pattern and induction of differentiation. E2-2 silencing phenocopies Id2 overexpression in MLL-AF9-AML cells. To study the gene expression changes associated with E2-2 depletion in the context of MLL-rearranged AML, RNA sequencing analysis was performed on MLL-AF9;NRAS AML cells transduced with vectors expressing hairpins against E2-2 (shTcf4#654 and shTcf4#3646) or a control hairpin against Renilla luciferase (shRen). Primary AMLs driven by MLL/AF9 expression linked to cherry reporter, in association with oncogenic NRASG12D (MLL/AF9;NRAS) were generated by reconstituting lethally irradiated congenic mice with fetal liver cells co-transduced with the MSCV-MLL/AF9-IRES-cherry retroviral vector and a second vector co-expressing NRASG12D together with luciferase (MSCV-luciferase-IRES-NRASG12D). RNA sequencing analysis sequencing analysis was performed on MLL-AF9;NRAS AML cells transduced in vitro with vectors expressing hairpins against E2-2 (shTcf4#654 and shTcf4#3646) or a control hairpin against Renilla luciferase (shRen) linked to the reporter GFP. Viable GFP-positive cells were FACS-sorted 2 days after transduction and used for RNA sequencing analysis. Two independent biological replicates of the experiment were used for the RNA sequencing (9-5-14 and 14-4-14).

2016-06-29 | E-GEOD-80745 | biostudies-arrayexpress

RNA-seq profiling of murine Tet-off MLL-AF9; NRAS acute myeloid leukemia at different timepoints upon doxycycline-induced MLL-AF9 down-regulation.

Project description:Using an acute myeloid leukemia (AML) mouse model driven by tet-regulated MLL-AF9 (fusion between the gene MLL1 (KMT2A/MLL) and MLLT3 (AF9)) co-expressed with oncogenic NRASG12D (Tet-off MLL-AF9), we investigated the effect of modulating the expression of the MLL-AF9 fusion oncogene on the transcriptome and proteome of established murine AML. Treatment in vitro or in vivo of these Tet-off MLL-AF9 AMLs with doxycycline (DOX) results in the efficient down-regulation of the expression of the driver oncogene MLL-AF9. RNA sequencing analysis was performed on primary Tet-Off MLL-AF9 AML cells obtained from the spleen of leukemic animals and cultured in vitro for either 2 or 4 days in the presence of doxycycline (1μg/ml) (DOX= down-regulation of MLL-AF9) or left untreated (UT).

2021-12-31 | GSE108326 | GEO

RNA sequencing expression analysis of murine MLL-AF9;NRAS acute myeloid leukemia cells silenced for E2-2.

2016-06-29 | GSE80745 | GEO

NRASG12V mediates leukemia self renewal [RNA-Seq]

Project description:Mutant RAS oncoproteins activate signaling molecules that drive oncogenesis in multiple human tumors including acute myelogenous leukemia (AML). However, the specific function of these pathways in AML is unclear. To elucidate the downstream functions of activated NRAS in AML, we employed a murine model of AML harboring Mll-AF9 and NRASG12V. We found that NRASG12V enforced leukemia self-renewal gene expression signatures and was required to maintain an MLL-AF9 and MYB-dependent gene expression program. In a multiplexed analysis of RAS-dependent signaling intermediates, the leukemia stem cell compartment was preferentially sensitive to RAS withdrawal. Use of RAS-pathway inhibitors showed that NRASG12V maintained leukemia self-renewal through mTOR and MEK pathway activation, implicating these pathways as potential targets for cancer stem cell-specific therapies. Mice harboring NRASG12V/Mll-AF9 AML were treated with doxycyline to abolish NRASG12V expression. Leukemia samples were harvested at 24 hour intervals after doxycyline treatment.

2014-11-16 | E-GEOD-49088 | biostudies-arrayexpress

RNA sequencing expression analysis of murine Tet-off MLL-AF9;NRAS acute myeloid leukemia cells over-expressing Id2 and upon MLL-AF9 withdrawal

Project description:We investigated the role of the transcriptional regulator Id2 in the context of MLL-rearranged acute myeloid leukemia (AML). Using an AML mouse model driven by tet-regulated MLL-AF9 co-expressed with oncogenic NRASG12D (Tet-off MLL-AF9), we demonstrated that MLL-AF9 regulates the E protein pathway by suppressing Id2, while activating the expression of its target E2-2. Moreover, we found that Id2 over-expression in Tet-Off MLL-AF9 AML cells in vitro partially phenocopies MLL-AF9 depletion and results inhibition of leukemia growth, loss of leukemia stem cell-associated gene expression pattern and induction of differentiation. To compare gene expression changes associated with enforced Id2 expression and MLL-AF9 withdrawal, RNA sequencing analysis was performed on Tet-off MLL-AF9 cells transduced with an Id2 over-expressing or a control vector, or upon MLL-AF9 dox-inducible knock-down. Primary AMLs driven by Tet-off inducible MLL/AF9 expression linked to dsRED reporter, in association with oncogenic NRASG12D (Tet-off MLL-AF9) were generated by reconstituting lethally irradiated congenic mice with foetal liver cells co-transduced with a Tet-Off-MLL-AF9-dRED retroviral vector and a second vector co-expressing NRASG12D together with the Tet-Off responsive transcriptional activator. RNA sequencing analysis sequencing analysis was performed on Tet-Off MLL-AF9/dsRED+ AML cells treated in vitro with doxycycline (DOX) for 4 days to inactivate MLL-AF9 expression or left untreated (UT). For the Id2 over-expression experiment, Tet-Off MLL-AF9/dsRED+ AML cells were transduced in vitro with an Id2-GFP or a control-GFP retroviral vector. Viable GFP-positive cells were FACS-sorted 2 days after transduction and used for RNA sequencing analysis.

2016-06-29 | E-GEOD-68462 | biostudies-arrayexpress

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