ArrayExpress Uploader0humantransfected with plasmid containing control GFPtransfected with plasmid containing wild type PML-RARα cDNA (pEGFP-PRWT )transfected with plasmid containing wild type PML-RARα cDNA (pEGFP-PR2VR )transfected with plasmid containing control GFPtransfected with plasmid containing wild type PML-RARα cDNA (pEGFP-PRWT )transfected with plasmid containing wild type PML-RARα cDNA (pEGFP-PR2VR )transfected with plasmid containing control GFPtransfected with plasmid containing wild type PML-RARα cDNA (pEGFP-PRWT )transfected with plasmid containing wild type PML-RARα cDNA (pEGFP-PR2VR )transfected with plasmid containing control GFPtransfected with plasmid containing wild type PML-RARα cDNA (pEGFP-PRWT )transfected with plasmid containing wild type PML-RARα cDNA (pEGFP-PR2VR )3644arrayexpress_sid4Previous studies in our laboratory demonstrated that the azurophil granule protease neutrophil elastase (NE) cleaves PML-RARA (PR), the...E-GEOD-21550/profile/8773/arrayexpressuploader112azurophil granulediseaseleukemiamedianneutrophilproteinDec.12, 2014Falseeffect-of-protease-resistant-pml-rar-on-the-leukemE-GEOD-21550_A-AFFY-44Effect of Protease-resistant PML-RARα on the leukemogenic potential in a mouse model of Acute Promyelocytic LeukemiaSep.15, 2014Previous 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 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.http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-21550http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-21550/samples/