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Mus musculus

ABSTRACT: AML1/ETO accelerates cell migration and impairs cell-to-cell adhesion and homing of hematopoietic stem/progenitor cells

PROVIDER: PRJNA309670 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR3115370_1.fastq.gz	Fastqsanger.gz
	SRR3115370_2.fastq.gz	Fastqsanger.gz
	SRR3115371_1.fastq.gz	Fastqsanger.gz
	SRR3115371_2.fastq.gz	Fastqsanger.gz
	SRR3115372_1.fastq.gz	Fastqsanger.gz

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AML1/ETO accelerates cell migration and impairs cell-to-cell adhesion and homing of hematopoietic stem/progenitor cells

Project description:The AML1/ETO fusion protein found in acute myeloid leukemias functions as a transcriptional regulator by recruiting co-repressor complexes to its DNA binding site. In order to extend the understanding of its role in preleukemia, we expressed AML1/ETO in a murine immortalized pluripotent hematopoietic stem/progenitor cell line, EML C1, and found that genes involved in functions such as cell-to-cell adhesion and cell motility were among the most significantly regulated as determined by RNA sequencing. In functional assays, AML1/ETO-expressing cells showed a decrease in adhesion to stromal cells, an increase of cell migration rate in vitro, and displayed an impairment in homing and engraftment in vivo upon transplantation into recipient mice. Our results suggest that AML1/ETO expression determines a more mobile and less adherent phenotype in preleukemic cells, therefore altering the interaction with the hematopoietic niche, potentially leading to the migration across the bone marrow barrier and to disease progression.

2016-10-07 | GSE77185 | GEO

PLCG1 is required for AML1-ETO leukemia stem cell self-renewal

Project description:In an effort to identify novel drugs targeting fusion-oncogene induced acute myeloid leukemia (AML), we performed high-resolution proteomic analysis. In AML1-ETO (AE) driven AML we uncovered a deregulation of phospholipase C (PLC) signaling. We identified PLCgamma 1 (PLCG1) as a specific target of the AE fusion protein which is induced after AE binding to intergenic regulatory DNA elements. Genetic inactivation of PLCG1 in murine and human AML inhibited AML1-ETO dependent self-renewal programs, leukemic proliferation, and leukemia maintenance in vivo. In contrast, PLCG1 was dispensable for normal hematopoietic stem- and progenitor cell function. These findings are extended to and confirmed by pharmacologic perturbation of Ca++-signaling in AML1-ETO AML cells, indicating that the PLCG1 pathway poses an important therapeutic target for AML1-ETO positive leukemic stem cells.

2021-11-04 | PXD026374 | Pride

Gene expression data from human CD34+ cord blood cells infected with MIGR1, MIGR1-AML1-ETO or MIGR1-AML1-ETO∆NHR1

2011-07-19 | GSE28317 | GEO

Gene expression data from human CD34+ cord blood cells infected with MIGR1, MIGR1-AML1-ETO or MIGR1-AML1-ETO∆NHR1

Project description:Compare the gene expression profile among human CD34+ cord blood cells infected with MIGR1, MIGR1-AML1-ETO or MIGR1-AML1-ETO∆NHR1 AML1-ETO promotes the self-renewal of human hematopoietic stem/progenitor cells (HSPCs). We found deletion of NHR1 domain abrogates AML1-ETO induced expasion of HSPCs. GFP+CD34+ human cord blood cells were sorted by FACS 72 hours after the infection for RNA extraction and hybridyzation for Affymetrix microarrays.

2011-07-18 | E-GEOD-28317 | biostudies-arrayexpress

Binding pattern and chromatin modifications induced by AML1/ETO in human hematopoietic stem/progenitor cells

Project description:The AML1/ETO fusion protein, which is present in 10% to 15% of cases of acute myeloid leukemia, is known to repress myeloid differentiation genes through DNA binding and recruitment of chromatin-modifying proteins and transcription factors in target genes. ChIP-chip analysis of human hematopoietic stem/progenitor cells transduced with the AML1/ETO fusion gene enabled us to identify 1168 AML1/ETO target genes, 103 of which were co-occupied by HDAC1 and had lost the hyperacetylation at histone H4 marks and 264 of which showed a K9 trimethylation at histone H3. Enrichment of genes involved in hematopoietic differentiation and in specific signaling pathways was observed in the presence of these epigenetic modifications associated with an inactive chromatin status. Furthermore, AML1/ETO target genes had a significant correlation between the chromatin marks studied and transcriptional silencing. ChIP-chip comparison of human hematopoietic stem/progenitor cells (HSPCs) retrovirally transduced with the AML1/ETO fusion protein with HSPCs transduced with an empty vector (Mulloy et al., Blood, 2002) using antibodies tagging the AML1/ETO fusion protein, the HDAC1 protein, as well as H4Ac and H3K9m3 chromatin modifications.

2012-01-18 | E-GEOD-27663 | biostudies-arrayexpress

FOXO1 is an oncogenic mediator in AML1-ETO leukemia

Project description:Transcriptome analysis by RNAseq of human CD34+ hematopoietic stem and progenitor cells transduced with empty vector control(MIT), AML1-ETO (AE), wildtype FOXO1 (F WT) or FOXO1 DNA binding deficient mutant (F DB). We find wildtype FOXO1 partially recapitulates gene signature of AML1-ETO

2017-12-15 | GSE81084 | GEO

Global Identification of the miR-130a targetome in human HSPC Reveals a Novel Role for TBL1XR1 in Hematopoietic Stem Cell Self-Renewal and t(8;21) AML

Project description:Gene expression profiling and proteome analysis of normal and malignant hematopoietic stem cells have firmly established the existence of shared core stemness properties. However, the discordance between mRNA and protein signatures underscores an important role for post-transcriptional regulation by miRNAs in governing this critical nexus. Here, we identify miR-130a as a regulator of hematopoietic stem cell (HSC) self-renewal and lineage differentiation. Integration of mass spectrometry and chimeric AGO2 eCLIP-seq identify TBL1XR1 as a primary miR-130a target. TBL1XR1 loss of function impairs lymphoid differentiation and expands long-term (LT)-HSC. This post-transcriptional regulation by miR-130a is usurped in t(8;21) acute myeloid leukemia (AML). Reduction of miR-130a levels in t(8;21) AML cells results in altered chromatin binding and composition of the AML1-ETO complex, demonstrating that miR-130a is critical for maintaining the oncogenic molecular program mediated by AML1-ETO. Our study establishes that comprehensive identification of the miRNA targetome within primary tissue enables the discovery of novel genes and molecular networks underpinning stemness properties of normal and leukemic cells.

2024-06-22 | PXD027331 | Pride

AML1-ETO transduced human cord blood cells, CD34 selected, compared to normal cord blood cells, CD34 selected

Project description:AML1-ETO expression in normal human umbilical cord blood CD34+ cells leads to long-term proliferation of an early self-renewing primitive progenitor cell with multilineage potential and stem cell ability, but these cells do not induce leukemia in immunodeficient mice. This comparative microarray study was initiated to determine the differences in the transcriptome of AML-ETO-expressing CD34+ cells after extended culture in vitro, using normal cord blood cells expanded for 6-8 weeks in vitro and subsequently purified for the CD34+ population as the control comparison. Keywords: Disease state analysis; comparison of changes in transcriptome due to long-term AML1-ETO expression in normal human hematopoietic CD34+ progenitor cells

2007-12-20 | GSE8023 | GEO

Targeting fatty acid metabolism to abrogate differentiation block in pre-leukemia induced by AML1-ETO

Project description:To gain the underlying insight into the functional impact of AML1-ETO expressed in HSPCs, RNA-seq was performed on purified LT-HSCs and GMPs from the bone marrow (BM) of both AML1-ETO expressed (AML1/ETO) and Wild-Type (control) C57 mice. Our work suggested that AML1-ETO resulted in impaired hematopoietic reconstitution and increased self-renewal ability.The oxidative phosphorylation and glycolysis decreased significantly in AML1/ETO LT-HSCs accompanied by increased HSC quiescence and reduced cell cycling. Furthermore, it was observed that HSCs expressing AML1-ETO exhibited an increased requirement for fatty acids when they differentiated.

2024-06-26 | GSE270447 | GEO

Binding pattern and chromatin modifications induced by AML1/ETO in human hematopoietic stem/progenitor cells

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