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Title: Effect of genetic Zfx deletion on gene expression in Notch induced T-ALL      
dateReleased:
01-30-2014
description:
Acute myeloid leukemia (AML) and acute T-lymphoblastic leukemia (T-ALL) maintain the undifferentiated phenotype and proliferative capacity of their respective cells of origin, hematopoietic stem/progenitor cells and immature thymocytes. The mechanisms that maintain these progenitor-like characteristics are poorly understood. We report that the transcription factor Zfx is required for the development and propagation of experimental AML caused by MLL-AF9 fusion, and of T-ALL caused by Notch1 activation. In both leukemia types, Zfx activated progenitor-associated gene expression programs and prevented differentiation. Key Zfx target genes included mitochondrial enzymes Ptpmt1 and Idh2, whose overexpression partially rescued the propagation of Zfx-deficient AML. These studies identify a common mechanism that controls the cell-of-origin characteristics of acute leukemias derived from disparate lineages and transformation mechanisms. Independent primary Notch induced T-ALL cell lines were created by retroviral transduction of Notch-IC into hematopoietic progenitors carrying the tamoxifen inducible Cre-ER transgene and the Zfx conditional (Zfx fl/y) allele (lines 14843, 14844, 14846). T-ALL cells generated from each line were isolated from moribund mice and transplanted into sublethally irradiated secondary recipients. Ten days after transplant when T-ALL cells had appeared in the blood of the secondary recipients, they were treated by gavage with either Vehicle or Tamoxifen (5 mg /day for three days) to induce Zfx deletion in leukemia cells. 48 hours after the final Tamoxifen treatment, the mice were sacrificed and T-ALL cells were recovered by FACS for microarray studies.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-43020
refinement:
raw
alternateIdentifiers:
43020
keywords:
functional genomics
dateModified:
02-18-2014
availability:
available
types:
gene expression
name:
Mus musculus
ID:
A-AFFY-130
name:
Affymetrix GeneChip Mouse Gene 1.0 ST Array [MoGene-1_0-st-v1]
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-43020/E-GEOD-43020.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-43020/E-GEOD-43020.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=GSE43020
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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