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Notch Pathway Activation Targets AML Cell Homeostasis and Differentiation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE42261 | GEO | 2013/01/18

SECONDARY ACCESSION(S): PRJNA179478

REPOSITORIES: GEO

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Notch Pathway Activation Targets AML Cell Homeostasis and Differentiation

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-01-18 | E-GEOD-42261 | biostudies-arrayexpress

Notch pathway activation targets AML-initiating cell homeostasis and differentiation.

Project description:Notch signaling pathway activation is known to contribute to the pathogenesis of a spectrum of human malignancies, including T cell leukemia. However, recent studies have implicated the Notch pathway as a tumor suppressor in myeloproliferative neoplasms and several solid tumors. Here we report a novel tumor suppressor role for Notch signaling in acute myeloid leukemia (AML) and demonstrate that Notch pathway activation could represent a therapeutic strategy in this disease. We show that Notch signaling is silenced in human AML samples, as well as in AML-initiating cells in an animal model of the disease. In vivo activation of Notch signaling using genetic Notch gain of function models or in vitro using synthetic Notch ligand induces rapid cell cycle arrest, differentiation, and apoptosis of AML-initiating cells. Moreover, we demonstrate that Notch inactivation cooperates in vivo with loss of the myeloid tumor suppressor Tet2 to induce AML-like disease. These data demonstrate a novel tumor suppressor role for Notch signaling in AML and elucidate the potential therapeutic use of Notch receptor agonists in the treatment of this devastating leukemia.

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Notch Pathway Activation Targets AML Cell Homeostasis and Differentiation: THP1 cell line

Project description:Expression data from untreated or Dll4-Fc treated THP1 cell line. We used Dll4-Fc stimulation of AML cells to study whether Notch activation has an impact on AML. We analyzed THP1 cell line in vitro treated with Dll4-Fc or vehicle control to determine genes affected by Notch activation. THP1 cell line was cultured on plate coated with 30 nM Dll4-Fc or vehicle for 48 hours prior to RNA extraction and hybridization to Human Genome U133 Plus 2.0 Affymetrix arrays.

2013-01-18 | E-GEOD-42259 | biostudies-arrayexpress

Notch Pathway Activation Targets AML Cell Homeostasis and Differentiation: MLL-AF9 transformed LGMP

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.

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Notch Pathway Activation Targets AML Cell Homeostasis and Differentiation: THP1 cell line

2013-01-18 | GSE42259 | GEO

Notch Pathway Activation Targets AML Cell Homeostasis and Differentiation: MLL-AF9 transformed LGMP

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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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