title: [The different characteristics of ABL kinase domain mutation in the Chinese Han nationality imatinib resistant Philadelphia chromosome-positive acute lymphoblastic leukemia and chronic myeloid leukemia].
abstract: OBJECTIVE
  To identify the distribution and differentiation of ABL kinase domain mutation in the Chinese Han nationality imatinib resistant chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL).
  
  
  METHODS
  Bone marrow or peripheral blood samples of 112 imatinib resistant CML patients and 21 Ph(+)ALL patients were obtained from the first affiliated hospital of Soochow university according to local law. Total RNA was extracted from the mononuclear cells using a TRIzol reagent. ABL kinase domain (KD) mutation was detected by direct sequencing.
  
  
  RESULTS
  Of the 112 imatinib resistant CML patients, 54.46%(61 cases) had ABL KD mutation. Twenty-three mutants were identified in 20 amino acid sites and 23.21% (26 cases) ABL KD mutations were in P-loop region. ABL KD mutations were also detected in 71.43% (15 cases) imatinib resistant Ph(+)ALL patients, with 10 mutations in 8 amino acid sites. The most frequent mutation was T315I (28.57%), followed by E255K/V (19.05%) and Y253F/H (14.29%). The frequency of T315I was much higher in imatinib resistant Ph(+) ALL than that in imatinib resistant CML (P = 0.001). Ph(+)ALL with additional chromosomal aberrations also had a higher rate of ABL KD mutation than that of CML (P = 0.010). Ph(+)ALL gained ABL KD mutation faster than CML (P < 0.010).
  
  
  CONCLUSIONS
  Chinese imatinib resistant CML and Ph(+)ALL patients had different characteristics in ABL KD mutation. The rate of ABL KD mutation in Ph(+)ALL with additional chromosomal aberrations was much higher than that of CML with additional chromosomal aberrations.
authors.affiliation: Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis, Soochow, China.
authors.forename: Hong-jie
authors.initials: HJ
authors.lastname: Shen
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.forename: Qiao-cheng
authors.initials: QC
authors.lastname: Qiu
authors.forename: Jian-nong
authors.initials: JN
authors.lastname: Cen
authors.forename: Jin-lan
authors.initials: JL
authors.lastname: Pan
authors.forename: Li
authors.initials: L
authors.lastname: Yao
authors.forename: Zi-xuan
authors.initials: ZX
authors.lastname: Ding
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Zi-xing
authors.initials: ZX
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D001549:Benzamides / Q000494:pharmacology; D002869:Chromosome Aberrations; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000494:pharmacology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics*; D011743:Pyrimidines / Q000494:pharmacology; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl