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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 01, 2010 |
| Title |
Effect of Protease-resistant PML-RARĪ± on the leukemogenic potential in a mouse model of Acute Promyelocytic Leukemia |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Previous studies in our laboratory demonstrated that the azurophil granule protease neutrophil elastase (NE) cleaves PML-RARA (PR), the fusion protein that initiates acute promyelocytic leukemia (APL). Further, NE deficiency reduces the penetrance of APL in a murine model of this disease. We therefore predicted that NE-mediated PR cleavage might be important for its ability to initiate APL. To test this hypothesis, we generated a mouse expressing NE-resistant PR. These mice developed APL indistinguishable from wild type PR, but with significantly reduced latency (median leukemia-free survival of 274 days versus 473 days for wild type PR, p<0.001). Resistance to proteolysis may increase the abundance of full length PR protein in early myeloid cells, and our previous data suggested that non-cleaved PR may be less toxic to early myeloid cells. Together, these effects appear to increase the leukemogenicity of NE-resistant PR, contrary to our previous prediction. We conclude that NE deficiency may reduce APL penetrance via indirect mechanisms that are still NE dependent.
Keywords: Time course
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| Overall design |
U937 cells were transfected with one of three tagged constructs GFP,GFP-PR,GFP-PR-2VR sorted for GFP positivity at the indicated time points and harvested for RNA.
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| Contributor(s) |
Uy GL, Ley TJ |
| Citation(s) |
20647568 |
| Submission date |
Apr 27, 2010 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Rekha Meyer |
| E-mail(s) |
rmeyer@pathbox.wustl.edu
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| Phone |
314 362 8853
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| Organization name |
Washington University School of Medicine
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| Street address |
4320 Forest Park Av
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| City |
St Louis |
| State/province |
MO |
| ZIP/Postal code |
63128 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (12)
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| GSM538607 |
U937 transfected with control GFP, 9 hours post transfection, replicate 1 |
| GSM538608 |
U937 transfected with GFP-PRWT,9 hours post infection, replicate 1 |
| GSM538609 |
U937 transfected with GFP-PR2VR, 9 hours post infection, replicate 1 |
| GSM538610 |
U937 transfected with control GFP, 6 hours post transfection, replicate 1 |
| GSM538611 |
U937 transfected with GFP-PRWT,6 hours post infection, replicate 1 |
| GSM538612 |
U937 transfected with GFP-PR2VR, 6 hours post infection, replicate 1 |
| GSM538613 |
U937 transfected with control GFP, 6 hours post transfection, replicate 2 |
| GSM538614 |
U937 transfected with GFP-PRWT,6 hours post infection, replicate 2 |
| GSM538615 |
U937 transfected with GFP-PR2VR, 6 hours post infection, replicate 2 |
| GSM538616 |
U937 transfected with control GFP, 9 hours post transfection, replicate 2 |
| GSM538617 |
U937 transfected with GFP-PRWT,9 hours post infection, replicate 2 |
| GSM538618 |
U937 transfected with GFP-PR2VR, 9 hours post infection, replicate 2 |
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| Relations |
| BioProject |
PRJNA126217 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE21550_RAW.tar |
59.3 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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