title: Imatinib mesylate resistance in a chronic myeloid leukemia patient with a novel e8a2 BCR-ABL transcript variant.
abstract: BACKGROUND
  The vast majority of chronic myeloid leukemia (CML) patients express the BCR-ABL transcript with the b2a2 (e13a2) and/or b3a2 (e14a2) junctions. However, some rare cases have atypical breakpoints.
  
  
  RESULTS
  We identified a CML patient with a unique e8a2 BCR-ABL transcript variant. It contained the first 114 nucleotides of BCR exon 8, with an insertion of 16 nucleotides from the 3' end of ABL intron 1a, followed by ABL exon 2. Due to her uncontrolled thrombocytosis after 3 years of interferon-alpha treatment, the patient received imatinib at a dosage of 400 mg/day. Though achieving a sustained and complete hematological response after 3 months, she was resistant to imatinib during the entire 65-month imatinib treatment. That is, she failed to achieve major cytogenetic response and there was no significant decrease in her BCR-ABL transcript levels. Meanwhile, an M351T mutant was detected at 18 months after the start of imatinib treatment.
  
  
  CONCLUSIONS
  ABL point mutation is also a mechanism of imatinib resistance for CML patients with the BCR-ABL transcript variant.
authors.affiliation: Peking University Institute of Hematology, Peking University People's Hospital, Beijing, People's Republic of China.
authors.forename: Ya Zhen
authors.initials: YZ
authors.lastname: Qin
authors.forename: Bin
authors.initials: B
authors.lastname: Jiang
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.forename: Jin Lan
authors.initials: JL
authors.lastname: Li
authors.forename: Hong Hu
authors.initials: HH
authors.lastname: Zhu
authors.forename: Ling Di
authors.initials: LD
authors.lastname: Li
authors.forename: Yan Rong
authors.initials: YR
authors.lastname: Liu
authors.forename: Shan Shan
authors.initials: SS
authors.lastname: Chen
authors.forename: Xiao Jun
authors.initials: XJ
authors.lastname: Huang
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001549:Benzamides; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D007155:Immunologic Factors / Q000008:administration & dosage; D016898:Interferon-alpha / Q000008:administration & dosage; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D010879:Piperazines / Q000008:administration & dosage*; D017354:Point Mutation; D011743:Pyrimidines / Q000008:administration & dosage*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D007155:Immunologic Factors; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl