{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360574095119376256.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1182/blood-2005-07-2815"}},{"identifier":{"@type":"URI","@value":"http://ashpublications.org/blood/article-pdf/108/1/319/470617/zh801306000319.pdf"}},{"identifier":{"@type":"NAID","@value":"30022499529"}}],"dc:title":[{"@value":"BCR/ABL kinase induces self-mutagenesis via reactive oxygen species to encode imatinib resistance"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Mutations in the BCR/ABL kinase domain play a major role in resistance to imatinib mesylate (IM). We report here that BCR/ABL kinase stimulates reactive oxygen species (ROS), which causes oxidative DNA damage, resulting in mutations in the kinase domain. The majority of mutations involved A/T→G/C and G/C→A/T transitions, a phenotype detected previously in patients, which encoded clinically relevant amino acid substitutions, causing IM resistance. This effect was reduced in cells expressing BCR/ABL(Y177F) mutant, which does not elevate ROS. Inhibition of ROS in leukemia cells by the antioxidants pyrrolidine dithiocarbamate (PDTC), N-acetylcysteine (NAC), and vitamin E (VE) decreased the mutagenesis rate and frequency of IM resistance. Simultaneous administration of IM and an antioxidant exerted better antimutagenic effect than an antioxidant alone. Therefore, inhibition of ROS should diminish mutagenesis and enhance the effectiveness of IM. (Blood. 2006;108:319-327)</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380574095119376258","@type":"Researcher","foaf:name":[{"@value":"Mateusz Koptyra"}],"jpcoar:affiliationName":[{"@value":"From the Department of Microbiology and Immunology, School of Medicine and the Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA; the Department of Immunology, The Medical University of Warsaw, Poland; and the Department of Molecular Genetics, University of Lodz, Poland."}]},{"@id":"https://cir.nii.ac.jp/crid/1380574095119376259","@type":"Researcher","foaf:name":[{"@value":"Rafal Falinski"}],"jpcoar:affiliationName":[{"@value":"From the Department of Microbiology and Immunology, School of Medicine and the Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA; the Department of Immunology, The Medical University of Warsaw, Poland; and the Department of Molecular Genetics, University of Lodz, Poland."}]},{"@id":"https://cir.nii.ac.jp/crid/1380574095119376256","@type":"Researcher","foaf:name":[{"@value":"Michal O. Nowicki"}],"jpcoar:affiliationName":[{"@value":"From the Department of Microbiology and Immunology, School of Medicine and the Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA; the Department of Immunology, The Medical University of Warsaw, Poland; and the Department of Molecular Genetics, University of Lodz, Poland."}]},{"@id":"https://cir.nii.ac.jp/crid/1380574095119376257","@type":"Researcher","foaf:name":[{"@value":"Tomasz Stoklosa"}],"jpcoar:affiliationName":[{"@value":"From the Department of Microbiology and Immunology, School of Medicine and the Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA; the Department of Immunology, The Medical University of Warsaw, Poland; and the Department of Molecular Genetics, University of Lodz, Poland."}]},{"@id":"https://cir.nii.ac.jp/crid/1380574095119376262","@type":"Researcher","foaf:name":[{"@value":"Ireneusz Majsterek"}],"jpcoar:affiliationName":[{"@value":"From the Department of Microbiology and Immunology, School of Medicine and the Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA; the Department of Immunology, The Medical University of Warsaw, Poland; and the Department of Molecular Genetics, University of Lodz, Poland."}]},{"@id":"https://cir.nii.ac.jp/crid/1380574095119376260","@type":"Researcher","foaf:name":[{"@value":"Margaret Nieborowska-Skorska"}],"jpcoar:affiliationName":[{"@value":"From the Department of Microbiology and Immunology, School of Medicine and the Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA; the Department of Immunology, The Medical University of Warsaw, Poland; and the Department of Molecular Genetics, University of Lodz, Poland."}]},{"@id":"https://cir.nii.ac.jp/crid/1380574095119376263","@type":"Researcher","foaf:name":[{"@value":"Janusz Blasiak"}],"jpcoar:affiliationName":[{"@value":"From the Department of Microbiology and Immunology, School of Medicine and the Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA; the Department of Immunology, The Medical University of Warsaw, Poland; and the Department of Molecular Genetics, University of Lodz, Poland."}]},{"@id":"https://cir.nii.ac.jp/crid/1380574095119376261","@type":"Researcher","foaf:name":[{"@value":"Tomasz Skorski"}],"jpcoar:affiliationName":[{"@value":"From the Department of Microbiology and Immunology, School of Medicine and the Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA; the Department of Immunology, The Medical University of Warsaw, Poland; and the Department of Molecular Genetics, University of Lodz, Poland."}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00064971"},{"@type":"EISSN","@value":"15280020"}],"prism:publicationName":[{"@value":"Blood"}],"dc:publisher":[{"@value":"American Society of Hematology"}],"prism:publicationDate":"2006-07-01","prism:volume":"108","prism:number":"1","prism:startingPage":"319","prism:endingPage":"327"},"reviewed":"false","url":[{"@id":"http://ashpublications.org/blood/article-pdf/108/1/319/470617/zh801306000319.pdf"}],"createdAt":"2006-03-09","modifiedAt":"2024-02-03","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1390001204273161600","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Current state and the future of molecular target drugs: lessons learned from the success of imatinib"},{"@language":"ja","@value":"Ｉｍａｔｉｎｉｂの成功に学ぶ分子標的治療薬の現状と将来"},{"@value":"治療薬シリーズ(32)標的分子薬(3-2)Imatinibの成功に学ぶ分子標的治療薬の現状と将来"},{"@language":"ja-Kana","@value":"チリョウヤク シリーズ 32 ヒョウテキ ブンシヤク 3 2 Imatinib ノ セイコウ ニ マナブ ブンシ ヒョウテキ チリョウヤク ノ ゲンジョウ ト ショウライ"}]},{"@id":"https://cir.nii.ac.jp/crid/1571980075407994752","@type":"Article","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@language":"ja","@value":"慢性骨髄性白血病細胞におけるパルス磁気刺激の効果"},{"@language":"en","@value":"Effects of pulsed magnetic stimulation on chronic myelogenous leukemia cells"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1182/blood-2005-07-2815"},{"@type":"CIA","@value":"30022499529"},{"@type":"CROSSREF","@value":"10.1254/fpj.132.339_references_DOI_P99tiIJOy5m0naCtumYKWjXIkzz"}]}