title: Detection of ABL1 kinase mutations in Philadelphia-positive patients exhibiting an inadequate molecular response using restriction fragment mass polymorphism and its clinical significance: a single-center experience in Korea.
abstract: BACKGROUND
  ABL1 kinase mutations represent a major mechanism of imatinib resistance in Philadelphia-positive (Ph+) patients. There is a paucity of data on ABL1 kinase mutations in Ph+ patients in Korea.
  
  
  METHODS
  We used restriction fragment mass polymorphism (RFMP) analysis to detect ABL1 kinase mutations in blood or bone marrow specimens from 80 Ph+ patients.
  
  
  RESULTS
  Fifty-seven patients met the criteria for inadequate molecular response (IMR). ABL1 kinase mutations were found in 2.6% of patients with chronic-phase chronic myelogenous leukemia (CML), 25.0% of accelerated-phase CML, 66.7% of blast-phase CML, and in 58.3% with Ph+ acute lymphoblastic leukemia. Twelve mutations were identified: 7 T315I, 2 E255V, 1 E255K, 1 F359V, and 1 Y253H. The majority of mutation-positive patients showed an unfavorable clinical course and often had an extra Ph or additional chromosomal abnormalities. Mutations were detected in two patients who had very low or absent BCR-ABL1 normalized ratios.
  
  
  CONCLUSIONS
  Mutation analysis should be performed in Ph+ patients exhibiting an IMR to imatinib. RFMP analysis is helpful for revising therapeutic strategies because it can sensitively detect clinically relevant ABL1 kinase mutations with high frequencies.
authors.affiliation: Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, South Korea.
authors.forename: Y-U
authors.initials: YU
authors.lastname: Cho
authors.forename: S-O
authors.initials: SO
authors.lastname: Kim
authors.forename: H-S
authors.initials: HS
authors.lastname: Chi
authors.forename: S-J
authors.initials: SJ
authors.lastname: Park
authors.forename: S
authors.initials: S
authors.lastname: Jang
authors.forename: C-J
authors.initials: CJ
authors.lastname: Park
authors.forename: E-J
authors.initials: EJ
authors.lastname: Seo
authors.forename: J-H
authors.initials: JH
authors.lastname: Lee
authors.forename: J-H
authors.initials: JH
authors.lastname: Lee
authors.forename: K-H
authors.initials: KH
authors.lastname: Lee
authors.forename: H-J
authors.initials: HJ
authors.lastname: Im
authors.forename: J-J
authors.initials: JJ
authors.lastname: Seo
authors.forename: S P
authors.initials: SP
authors.lastname: Hong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002869:Chromosome Aberrations; D003062:Codon; D004252:DNA Mutational Analysis; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D059785:Karyotype; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012150:Polymorphism, Restriction Fragment Length; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics*; D054730:Protein Interaction Domains and Motifs / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003062:Codon; D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl
keywords: ABL1 kinase mutation; inadequate molecular response; restriction fragment mass polymorphism