title: Detection of single nucleotide insertion of BCR/ABL region in imatinib-resistant human myelogenous leukemia SR-1 cells.
abstract: Imatinib mesylate is a selective Bcr/Abl kinase inhibitor and an effective anticancer agent for Bcr/Abl-positive chronic myelogenous leukemia. Most patients in chronic phase maintain durable responses; however, many in blast crisis fail to respond, or relapse quickly. Mutations within the BCR/ABL kinase domain are the most commonly identified mechanism associated with relapse. To overcome the imatinib resistance in CML, many investigators have tried to clarify molecular mechanism for imatinib resistance in cells of patients who failed to respond to imatinib. Our aim was to invesitigate underlying mechanism for imatinib resistance in SR-1 cells, which were derived from a CML patient in blast crisis. We detected the new mutation of BCR/ABL, resulting in premature termination and loss of BCR/ABL fusion protein expression, which might be possible mechanism for the resistance to imatinib in SR-1 cells.
authors.affiliation: Department of Internal Medicine, Dong-A University, College of Medicine, Busan 602-715, Korea.
authors.forename: Tae Ho
authors.initials: TH
authors.lastname: Park
authors.forename: Hyuk Chan
authors.initials: HC
authors.lastname: Kwon
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jin Yeong
authors.initials: JY
authors.lastname: Han
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Jeong
authors.forename: Hoon Yeon
authors.initials: HY
authors.lastname: Han
authors.forename: Chi
authors.initials: C
authors.lastname: Seo
authors.forename: Jong Young
authors.initials: JY
authors.lastname: Kwak
authors.forename: Joo In
authors.initials: JI
authors.lastname: Park
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001549:Benzamides; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D016044:Fusion Proteins, bcr-abl / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D007951:Leukemia, Myeloid / Q000235:genetics*; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000235:genetics*; D009711:Nucleotides / Q000235:genetics; D010879:Piperazines / Q000494:pharmacology*; D017354:Point Mutation / Q000235:genetics*; D011743:Pyrimidines / Q000494:pharmacology*
chemical_list: D001549:Benzamides; D009711:Nucleotides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl