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Title: Association of prognosis of acute myeloid leukemia patients with leukemia stem cell gene signature based on nucleostemin promoter activity      
dateReleased:
07-30-2014
description:
Acute myeloid leukemia (AML) is a heterogeneous neoplastic disorder, in which only a subset of cells have function as leukemia-initiating cells (LICs). In this study, we prospectively evaluated leukemia-initiating capacity of fractionated subpopulations of AML cells depending on expression of a nucleolar GTP binding protein, Nucleostemin (NS). To monitor NS expression in living AML cells, we generated a mouse AML model using a transgenic mouse, in which green florescence protein (GFP) is expressed under the control of particular region of NS promoter (NS-GFP). In AML cells, NS-GFP levels were correlated with endogenous NS mRNA. AML cells with the highest expression of NS-GFP were very immature blast-like cells, efficiently formed leukemia colonies in vitro, and exhibited high leukemia-initiating capacity in vivo. Gene expression profiling analysis revealed that cell cycle regulators and nucleotide metabolism-related genes were highly enriched in a gene set associated with leukemia-initiating capacity, i.e., leukemia stem cell gene signature. Furthermore, we found that the leukemia stem cell gene signature stratified human AML patients into two distinct clusters, reflecting prognosis. These data demonstrate that the mouse leukemia stem cell gene signature is significantly associated with malignant properties of human AML patients. Further analyses of gene regulation related with leukemia stem cells would provide novel insights for the progress in diagnostic and therapeutic approach of AML patients. A mouse acute myeloid leukemia model was generated by introduction of HoxA9/Meis1 to bone marrow cells from a transgenic mouse, in which green florescence protein (GFP) is expressed under the control of particular region of NS promoter (NS-GFP).The leukemia cells were fractionated into 4 subpopulations based on NS-GFP level and c-Kit expression, (a) c-Kit-NS-GFPlow, (b) c-Kit-NS-GFPmiddle, (c) c-Kit+NS-GFPmiddle and (d) c-Kit+NS-GFPhigh cells.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-58032
refinement:
raw
alternateIdentifiers:
58032
keywords:
functional genomics
dateModified:
08-02-2014
availability:
available
types:
gene expression
name:
Mus musculus
ID:
A-AFFY-45
name:
Affymetrix GeneChip Mouse Genome 430 2.0 [Mouse430_2]
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-58032/E-GEOD-58032.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-58032/E-GEOD-58032.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE58032
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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