Effect of genetic Zfx deletion on gene expression in c-Kit + MLL-AF9 AML cells
Transcriptomics Dataset
FAIR Metrics
1 evaluation
General Information
AccessionGSE36921
TitleEffect of genetic Zfx deletion on gene expression in c-Kit + MLL-AF9 AML cells
DescriptionAcute myeloid leukemia (AML) propagates as a cellular hierarchy which is maintained by a rare subpopulation of self-renewing leukemia-initiating cells (LICs). These LICs phenotypically resemble HSCs and early myeloid progenitors, and they are functionally defined by their ability to reconstitute AML in xenografted mice. Common transcriptional regulators are believed to drive self-renewal of LICs and normal stem cells. Examples include the histone methyltransferase, MLL and its main targets, the transcription factors HOXA9 and MEIS1; the polycomb group protein, BMI-1; and the Wnt/-catenin signaling pathway4-9. In AML patients, LICs have been shown to share broad gene expression signatures with hematopoietic stem cells (HSCs) and, in some cases, with embryonic stem cells (ESCs). Moreover, increased expression of these stem cell signatures has been linked to tumor aggressiveness. Elucidating the molecular determinants of stem cell properties in LICs has the potential to improve AML therapy and clarify the relationship between cancer and stem cell biology in general. Here we show that the propagation of LICs in AML depends on Zfx, a transcription factor required for the self-renewal of ESCs and HSCs. Using mouse models, we found that Zfx is required for AML propagation and LIC maintenance. We defined a Zfx-driven gene expression program in murine LICs that correlates with existing stem cell-related gene expression signatures in AML patients. Using a novel, stroma-based RNAi screening strategy, we identified functionally important Zfx target genes. Two of these genes FAM92A1 and DOCK7 - are required for human AML cell propagation; moreover, their expression levels strongly correlate with AML patient survival across the full spectrum of AML subtypes. Together, our results characterize a novel gene expression program that orchestrates critical stem cell properties of LICs, and drives aggressiveness of AML.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE36921
RepositoryGene Expression Omnibus
Tools used to analyze the dataset
Keyword
Dataset Accession
Enrichr
Published May 2016
A comprehensive gene set enrichment analysis web server 2016 update
7759
65
Characteristic Direction
Published March 2014
A geometrical multivariate approach to identify differentially expressed genes
26829
GeneMANIA
Published June 2010
Biological network integration for gene prioritization and predicting gene function
7435
L1000CDS2
Published August 2016
An ultra-fast LINCS L1000 Characteristic Direction signature search engine
7756
PAEA
Published November 2015
Enrichment analysis tool implementing the principal angle method
3879
Canned Analyses generated with the dataset
Filters  
Dataset Accession
Tool Name
Direction
Geneset
Small molecules which mimic ZFX KO
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse ZFX KO
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which rev...
Enrichment analysis of genes dysregulated in ZFX KO
PAEA, Characteristic Direction
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Interaction network and enrichment analysis of genes downregulated in ZFX KO
GeneMANIA, Characteristic Direction
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Interaction network and enrichment analysis of genes upregulated in ZFX KO
GeneMANIA, Characteristic Direction
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Enrichment analysis of genes downregulated in ZFX KO
Enrichr, Characteristic Direction
An enrichment analysis was performed on the top 500 most downregulated genes identified by...
Enrichment analysis of genes upregulated in ZFX KO
Enrichr, Characteristic Direction
An enrichment analysis was performed on the top 500 most upregulated genes identified by a...
FAIR Evaluation
Sorry, you must be signed in to evaluate this object.