| http://purl.uniprot.org/citations/18757400 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/18757400 | http://www.w3.org/2000/01/rdf-schema#comment | "Myeloproliferative disorders (MPD) are stem cell-derived clonal diseases arising as a consequence of acquired aberrations in c-ABL, Janus-activated kinase 2 (JAK2), and platelet-derived growth factor receptor (PDGFR) that generate oncogenic fusion tyrosine kinases (FTK), including BCR/ABL, TEL/ABL, TEL/JAK2, and TEL/PDGFbetaR. Here, we show that FTKs stimulate the formation of reactive oxygen species and DNA double-strand breaks (DSB) both in hematopoietic cell lines and in CD34(+) leukemic stem/progenitor cells from patients with chronic myelogenous leukemia (CML). Single-strand annealing (SSA) represents a relatively rare but very unfaithful DSB repair mechanism causing chromosomal aberrations. Using a specific reporter cassette integrated into genomic DNA, we found that BCR/ABL and other FTKs stimulated SSA activity. Imatinib-mediated inhibition of BCR/ABL abrogated this effect, implicating a kinase-dependent mechanism. Y253F, E255K, T315I, and H396P mutants of BCR/ABL that confer imatinib resistance also stimulated SSA. Increased expression of either nonmutated or mutated BCR/ABL kinase, as is typical of blast phase cells and very primitive chronic phase CML cells, was associated with higher SSA activity. BCR/ABL-mediated stimulation of SSA was accompanied by enhanced nuclear colocalization of RAD52 and ERCC1, which play a key role in the repair. Taken together, these findings suggest a role of FTKs in causing disease progression in MPDs by inducing chromosomal instability through the production of DSBs and stimulation of SSA repair."xsd:string |
| http://purl.uniprot.org/citations/18757400 | http://purl.org/dc/terms/identifier | "doi:10.1158/0008-5472.can-08-1101"xsd:string |
| http://purl.uniprot.org/citations/18757400 | http://purl.uniprot.org/core/author | "Cramer K."xsd:string |
| http://purl.uniprot.org/citations/18757400 | http://purl.uniprot.org/core/author | "Skorski T."xsd:string |
| http://purl.uniprot.org/citations/18757400 | http://purl.uniprot.org/core/author | "Nieborowska-Skorska M."xsd:string |
| http://purl.uniprot.org/citations/18757400 | http://purl.uniprot.org/core/author | "Slupianek A."xsd:string |
| http://purl.uniprot.org/citations/18757400 | http://purl.uniprot.org/core/author | "Eaves C.J."xsd:string |
| http://purl.uniprot.org/citations/18757400 | http://purl.uniprot.org/core/author | "Koptyra M."xsd:string |
| http://purl.uniprot.org/citations/18757400 | http://purl.uniprot.org/core/author | "Aulitzky W."xsd:string |
| http://purl.uniprot.org/citations/18757400 | http://purl.uniprot.org/core/author | "Penserga E.T."xsd:string |
| http://purl.uniprot.org/citations/18757400 | http://purl.uniprot.org/core/date | "2008"xsd:gYear |
| http://purl.uniprot.org/citations/18757400 | http://purl.uniprot.org/core/name | "Cancer Res"xsd:string |
| http://purl.uniprot.org/citations/18757400 | http://purl.uniprot.org/core/pages | "6884-6888"xsd:string |
| http://purl.uniprot.org/citations/18757400 | http://purl.uniprot.org/core/title | "BCR/ABL and other kinases from chronic myeloproliferative disorders stimulate single-strand annealing, an unfaithful DNA double-strand break repair."xsd:string |
| http://purl.uniprot.org/citations/18757400 | http://purl.uniprot.org/core/volume | "68"xsd:string |
| http://purl.uniprot.org/citations/18757400 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/18757400 |
| http://purl.uniprot.org/citations/18757400 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/18757400 |
| http://purl.uniprot.org/uniprot/#_P54132-mappedCitation-18757400 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18757400 |
| http://purl.uniprot.org/uniprot/#_Q14191-mappedCitation-18757400 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18757400 |
| http://purl.uniprot.org/uniprot/#_P49959-mappedCitation-18757400 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18757400 |
| http://purl.uniprot.org/uniprot/#_Q13472-mappedCitation-18757400 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18757400 |
| http://purl.uniprot.org/uniprot/#_Q13535-mappedCitation-18757400 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18757400 |
| http://purl.uniprot.org/uniprot/#_O75943-mappedCitation-18757400 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18757400 |
| http://purl.uniprot.org/uniprot/#_P38398-mappedCitation-18757400 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/18757400 |