| http://purl.uniprot.org/citations/15448205 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15448205 | http://www.w3.org/2000/01/rdf-schema#comment | "Human stem cell leukemia-lymphoma syndrome usually presents itself as a myeloproliferative disorder (MPD) that evolves to acute myeloid leukemia and/or lymphoma. The syndrome associated with t(8;13)(p11;q12) results in expression of the ZNF198-fibroblast growth factor receptor (FGFR) 1 fusion tyrosine kinase. Current empirically derived cytotoxic chemotherapy is inadequate for treatment of this disease. We hypothesized that small-molecule inhibitors of the ZNF198-FGFR1 fusion would have therapeutic efficacy. We characterized the transforming activity of ZNF198-FGFR1 in hematopoietic cells in vitro and in vivo. Expression of ZNF198-FGFR1 in primary murine hematopoietic cells caused a myeloproliferative syndrome in mice that recapitulated the human MPD phenotype. Transformation in these assays, and activation of the downstream effector molecules PLC-gamma, STAT5, and phosphatidylinositol 3-kinase/AKT, required the proline-rich domains, but not the ZNF domains, of ZNF198. A small-molecule tyrosine kinase inhibitor, PKC412 (N-benzoyl-staurosporine) effectively inhibited ZNF198-FGFR1 tyrosine kinase activity and activation of downstream effector pathways, and inhibited proliferation of ZNF198-FGFR1 transformed Ba/F3 cells. Furthermore, treatment with PKC412 resulted in statistically significant prolongation of survival in the murine model of ZNF198-FGFR1-induced MPD. Based in part on these data, PKC412 was administered to a patient with t(8;13)(p11;q12) and was efficacious in treatment of progressive myeloproliferative disorder with organomegaly. Therefore, PKC412 may be a useful therapy for treatment of human stem cell leukemia-lymphoma syndrome."xsd:string |
| http://purl.uniprot.org/citations/15448205 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.0404438101"xsd:string |
| http://purl.uniprot.org/citations/15448205 | http://purl.uniprot.org/core/author | "Chen J."xsd:string |
| http://purl.uniprot.org/citations/15448205 | http://purl.uniprot.org/core/author | "Meyer T."xsd:string |
| http://purl.uniprot.org/citations/15448205 | http://purl.uniprot.org/core/author | "Xiao S."xsd:string |
| http://purl.uniprot.org/citations/15448205 | http://purl.uniprot.org/core/author | "Cohen S."xsd:string |
| http://purl.uniprot.org/citations/15448205 | http://purl.uniprot.org/core/author | "Kutok J.L."xsd:string |
| http://purl.uniprot.org/citations/15448205 | http://purl.uniprot.org/core/author | "Fletcher J.A."xsd:string |
| http://purl.uniprot.org/citations/15448205 | http://purl.uniprot.org/core/author | "Fabbro D."xsd:string |
| http://purl.uniprot.org/citations/15448205 | http://purl.uniprot.org/core/author | "Gilliland D.G."xsd:string |
| http://purl.uniprot.org/citations/15448205 | http://purl.uniprot.org/core/author | "Lee B.H."xsd:string |
| http://purl.uniprot.org/citations/15448205 | http://purl.uniprot.org/core/author | "Wadleigh M."xsd:string |
| http://purl.uniprot.org/citations/15448205 | http://purl.uniprot.org/core/author | "Griffin J.D."xsd:string |
| http://purl.uniprot.org/citations/15448205 | http://purl.uniprot.org/core/author | "Cohen P.S."xsd:string |
| http://purl.uniprot.org/citations/15448205 | http://purl.uniprot.org/core/author | "Okabe R."xsd:string |
| http://purl.uniprot.org/citations/15448205 | http://purl.uniprot.org/core/author | "Duclos N."xsd:string |
| http://purl.uniprot.org/citations/15448205 | http://purl.uniprot.org/core/author | "Galinsky I."xsd:string |
| http://purl.uniprot.org/citations/15448205 | http://purl.uniprot.org/core/author | "Stone R.M."xsd:string |
| http://purl.uniprot.org/citations/15448205 | http://purl.uniprot.org/core/author | "Williams I.R."xsd:string |
| http://purl.uniprot.org/citations/15448205 | http://purl.uniprot.org/core/author | "Banerji L."xsd:string |
| http://purl.uniprot.org/citations/15448205 | http://purl.uniprot.org/core/author | "Adelsperger J."xsd:string |
| http://purl.uniprot.org/citations/15448205 | http://purl.uniprot.org/core/author | "Coburn A."xsd:string |
| http://purl.uniprot.org/citations/15448205 | http://purl.uniprot.org/core/author | "Deangelo D.J."xsd:string |
| http://purl.uniprot.org/citations/15448205 | http://purl.uniprot.org/core/author | "Huntly B."xsd:string |