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| Status |
Public on Jan 30, 2014 |
| Title |
Effect of genetic Zfx deletion on gene expression in Notch induced T-ALL |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
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.
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| Contributor(s) |
Weisberg SP, Reizis BV |
| Citation(s) |
24485662 |
| Submission date |
Dec 19, 2012 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Stuart Weisberg |
| E-mail(s) |
spw13@cumc.columbia.edu
|
| Organization name |
Columbia University
|
| Department |
Pathology and Cell Biology
|
| Lab |
Weisberg
|
| Street address |
650 W 168th Street
|
| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10032 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE43022 |
ZFX controls the propagation and cell-of-origin characteristics of acute leukemia |
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| Relations |
| BioProject |
PRJNA184064 |
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