Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA179480 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To determine role of Notch signaling in AML leukemia initiating cells we used a conditional mouse knock-in model of Notch1-IC to induce Notch1-IC expression in MLL-AF9 transformed LGMP. WT and Notch1-IC+ LGMP were analyzed to determined genes controlled by Notch signaling.
2013-01-18 | GSE42260 | GEO
Project description:Notch Pathway Activation Targets AML Cell Homeostasis and Differentiation: THP1 cell line
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Project description:Expression profiling of secondary wild type (WT) and Ezh2-null murine MLL-AF9 AML
2015-09-22 | E-GEOD-34961 | ExpressionAtlas
Project description:To determine role of Notch signaling in AML leukemia initiating cells we used a conditional mouse knock-in model of Notch1-IC to induce Notch1-IC expression in MLL-AF9 transformed LGMP. WT and Notch1-IC+ LGMP were analyzed to determined genes controlled by Notch signaling. 12 weeks old wt lethaly irradiated mice were transplanted with 50000 cKit+ MLL-AF9-IRES-YFP infected cells from MLL-AF9 EF1 wt/wt ROSAwt/CreERT2 or MLL-AF9 EF1 wt/lsl-N1-IC ROSAwt/CreERT2 mice + 250000 support wt total bone marrow cells. 4 weeks after transplant mice were injected 2 times with tamoxifen (0.2mg/g body weight) every other day. Mice were sacrificed and analyzed 6 days after last injection. LGMP were flow purified for RNA extraction and hybridization on Affymetrix microarrays.
2013-01-18 | E-GEOD-42260 | biostudies-arrayexpress
Project description:In leukemogenesis Notch signaling can be up- and down-regulated in a context-dependent manner. Here we report that deletion of hairy and enhancer of split-1 (Hes1) promotes acute myeloid leukemia (AML) development induced by the MLL-AF9 fusion protein. Subsequently, the FMS-like tyrosine kinase 3 (FLT3) was up-regulated in mouse cells of a Hes1- or RBP-J-null background. MLL-AF9-expressing Hes1-null AML cells showed enhanced proliferation and ERK phosphorylation following FLT3 ligand stimulation. FLT3 inhibition efficiently abrogated proliferation of MLL-AF9-induced Hes1-null AML cells. Furthermore, an agonistic anti-Notch2 antibody induced apoptosis of MLL-AF9-induced AML cells in a Hes1-wild type but not a Hes1-null background. These observations demonstrate that Hes1 mediates tumor suppressive roles of Notch signaling in AML development by down-regulating FLT3 expression. 4 samples are analyzed, two pairs of MLL-AF9/Hes1-/- and MLL-AF9/Hes1+/+ leukemic bone marrows.
2017-05-02 | E-GEOD-50234 | biostudies-arrayexpress
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. Primary NRASG12V-Mll-AF9 AML cells were treated in vitro for 24 hours with Ras-pathway inhibitors. RNA was extracted from these cells and submitted for RNA sequencing.
2014-11-16 | E-GEOD-49087 | biostudies-arrayexpress
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
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 12 hour intervals after doxycyline treatment. RNA was extracted from these samples and submitted for gene expression microarray analysis
2014-11-16 | E-GEOD-49038 | biostudies-arrayexpress
Project description:Expression profiling of primary wild type (WT), Ezh2-null and Eed-null murine MLL-AF9 AML
2015-09-22 | E-GEOD-34959 | ExpressionAtlas