Transcriptomics

Dataset Information

3

Effect of genetic Zfx deletion on gene expression in Notch induced T-ALL


ABSTRACT: 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.

ORGANISM(S): Mus musculus  

SUBMITTER: Boris V Reizis   Stuart P Weisberg  Stuart Weisberg 

PROVIDER: E-GEOD-43020 | ArrayExpress | 2014-01-30

SECONDARY ACCESSION(S): GSE43020PRJNA184064

REPOSITORIES: GEO, ArrayExpress

Dataset's files

Source:
Action DRS
E-GEOD-43020.idf.txt Idf
E-GEOD-43020.processed.1.zip Processed
E-GEOD-43020.raw.1.zip Raw
E-GEOD-43020.sdrf.txt Txt
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