| http://purl.uniprot.org/citations/27819671 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27819671 | http://www.w3.org/2000/01/rdf-schema#comment | "Eradication of leukemia stem cells (LSCs) is the ultimate goal of treating acute myeloid leukemia (AML). We recently showed that the combined loss of Runx1/Cbfb inhibited the development of MLL-AF9-induced AML. However, c-Kit+/Gr-1- cells remained viable in Runx1/Cbfb-deleted cells, indicating that suppressing RUNX activity may not eradicate the most immature LSCs. In this study, we found upregulation of several hemostasis-related genes, including the thrombin-activatable receptor PAR-1 (protease-activated receptor-1), in Runx1/Cbfb-deleted MLL-AF9 cells. Similar to the effect of Runx1/Cbfb deletion, PAR-1 overexpression induced CDKN1A/p21 expression and attenuated proliferation in MLL-AF9 cells. To our surprise, PAR-1 deficiency also prevented leukemia development induced by a small number of MLL-AF9 leukemia stem cells (LSCs) in vivo. PAR-1 deficiency also reduced leukemogenicity of AML1-ETO-induced leukemia. Re-expression of PAR-1 in PAR-1-deficient cells combined with a limiting-dilution transplantation assay demonstrated the cell-dose-dependent role of PAR-1 in MLL-AF9 leukemia: PAR-1 inhibited rapid leukemic proliferation when there were a large number of LSCs, while a small number of LSCs required PAR-1 for their efficient growth. Mechanistically, PAR-1 increased the adherence properties of MLL-AF9 cells and promoted their engraftment to bone marrow. Taken together, these data revealed a multifaceted role for PAR-1 in leukemogenesis, and highlight this receptor as a potential target to eradicate primitive LSCs in AML."xsd:string |
| http://purl.uniprot.org/citations/27819671 | http://purl.org/dc/terms/identifier | "doi:10.1038/onc.2016.416"xsd:string |
| http://purl.uniprot.org/citations/27819671 | http://purl.uniprot.org/core/author | "Miller W."xsd:string |
| http://purl.uniprot.org/citations/27819671 | http://purl.uniprot.org/core/author | "Shrestha M."xsd:string |
| http://purl.uniprot.org/citations/27819671 | http://purl.uniprot.org/core/author | "Kitamura T."xsd:string |
| http://purl.uniprot.org/citations/27819671 | http://purl.uniprot.org/core/author | "Mulloy J.C."xsd:string |
| http://purl.uniprot.org/citations/27819671 | http://purl.uniprot.org/core/author | "Goyama S."xsd:string |
| http://purl.uniprot.org/citations/27819671 | http://purl.uniprot.org/core/author | "O'Brien E."xsd:string |
| http://purl.uniprot.org/citations/27819671 | http://purl.uniprot.org/core/author | "Schibler J."xsd:string |
| http://purl.uniprot.org/citations/27819671 | http://purl.uniprot.org/core/author | "Palumbo J.S."xsd:string |
| http://purl.uniprot.org/citations/27819671 | http://purl.uniprot.org/core/author | "Mizukawa B."xsd:string |
| http://purl.uniprot.org/citations/27819671 | http://purl.uniprot.org/core/author | "Rosenfeldt L."xsd:string |
| http://purl.uniprot.org/citations/27819671 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/27819671 | http://purl.uniprot.org/core/name | "Oncogene"xsd:string |
| http://purl.uniprot.org/citations/27819671 | http://purl.uniprot.org/core/pages | "2589-2598"xsd:string |
| http://purl.uniprot.org/citations/27819671 | http://purl.uniprot.org/core/title | "Protease-activated receptor-1 inhibits proliferation but enhances leukemia stem cell activity in acute myeloid leukemia."xsd:string |
| http://purl.uniprot.org/citations/27819671 | http://purl.uniprot.org/core/volume | "36"xsd:string |
| http://purl.uniprot.org/citations/27819671 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/27819671 |
| http://purl.uniprot.org/citations/27819671 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/27819671 |
| http://purl.uniprot.org/uniprot/#_A0A087WPL0-mappedCitation-27819671 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27819671 |
| http://purl.uniprot.org/uniprot/#_A0A087WR05-mappedCitation-27819671 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27819671 |
| http://purl.uniprot.org/uniprot/#_A0A0C4DG58-mappedCitation-27819671 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27819671 |
| http://purl.uniprot.org/uniprot/#_A0A6M6RJQ2-mappedCitation-27819671 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27819671 |
| http://purl.uniprot.org/uniprot/#_A0A7D4XPZ8-mappedCitation-27819671 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27819671 |