NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE21550 Query DataSets for GSE21550
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
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
 
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.
 
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
Phone 314 362 8853
Organization name Washington University School of Medicine
Street address 4320 Forest Park Av
City St Louis
State/province MO
ZIP/Postal code 63128
Country USA
 
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (12)
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
Relations
BioProject PRJNA126217

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE21550_RAW.tar 59.3 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap