{"owner": "ArrayExpress Uploader", "pop_total": 0, "species": "human", "factors": [{"GSM538607": {"TRANSFECTANT": "transfected with plasmid containing control GFP"}}, {"GSM538608": {"TRANSFECTANT": "transfected with plasmid containing wild type PML-RAR\u03b1 cDNA (pEGFP-PRWT )"}}, {"GSM538609": {"TRANSFECTANT": "transfected with plasmid containing wild type PML-RAR\u03b1 cDNA (pEGFP-PR2VR )"}}, {"GSM538607": {"TRANSFECTANT": "transfected with plasmid containing control GFP"}}, {"GSM538608": {"TRANSFECTANT": "transfected with plasmid containing wild type PML-RAR\u03b1 cDNA (pEGFP-PRWT )"}}, {"GSM538609": {"TRANSFECTANT": "transfected with plasmid containing wild type PML-RAR\u03b1 cDNA (pEGFP-PR2VR )"}}, {"GSM538607": {"TRANSFECTANT": "transfected with plasmid containing control GFP"}}, {"GSM538608": {"TRANSFECTANT": "transfected with plasmid containing wild type PML-RAR\u03b1 cDNA (pEGFP-PRWT )"}}, {"GSM538609": {"TRANSFECTANT": "transfected with plasmid containing wild type PML-RAR\u03b1 cDNA (pEGFP-PR2VR )"}}, {"GSM538607": {"TRANSFECTANT": "transfected with plasmid containing control GFP"}}, {"GSM538608": {"TRANSFECTANT": "transfected with plasmid containing wild type PML-RAR\u03b1 cDNA (pEGFP-PRWT )"}}, {"GSM538609": {"TRANSFECTANT": "transfected with plasmid containing wild type PML-RAR\u03b1 cDNA (pEGFP-PR2VR )"}}], "id": 3644, "ownerprofile_id": "arrayexpress_sid", "platform": 4, "summary_wrapped": "Previous studies in our laboratory demonstrated that the azurophil granule protease neutrophil elastase (NE) cleaves PML-RARA (PR), the...", "geo_gse_id": "E-GEOD-21550", "owner_profile": "/profile/8773/arrayexpressuploader", "factor_count": 1, "sample_count": 12, "tags": ["azurophil granule", "disease", "leukemia", "median", "neutrophil", "protein"], "lastmodified": "Dec.12, 2014", "is_default": false, "geo_gds_id": "", "slug": "effect-of-protease-resistant-pml-rar-on-the-leukem", "geo_id_plat": "E-GEOD-21550_A-AFFY-44", "name": "Effect of Protease-resistant PML-RAR\u03b1 on the leukemogenic potential in a mouse model of Acute Promyelocytic Leukemia", "created": "Sep.15, 2014", "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 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.", "source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-21550", "sample_source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-21550/samples/"}