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| Status |
Public on Jan 30, 2014 |
| Title |
Effect of genetic Zfx deletion on Myc induced gene expression in bone marrrow myeloid progenitors |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| 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 |
Bone marrow progenitors (c-Kit +) from Zfx wt/y CreER mice and Zfx fl/y CreER mice were harvested after tamoxifen administration to induce Cre. The Zfx wt and Zfx ko progenitors were infected with Myc expressing and control retrovirus with GFP selectable marker and cultured for 48 hours in cytokine supplemented media. The GFP + myeloid progenitors were sorted and cultured for another 4 days prior to RNA extraction.
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| Contributor(s) |
Weisberg SP, Reizis BV |
| Citation missing |
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| Submission date |
Nov 15, 2013 |
| 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 (12)
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| This SubSeries is part of SuperSeries: |
| GSE43022 |
ZFX controls the propagation and cell-of-origin characteristics of acute leukemia |
|
| Relations |
| BioProject |
PRJNA228194 |
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