title: [Correlation between point mutation in ABL kinase and clinical outcome of chronic myeloid leukemia patients].
abstract: OBJECTIVE
  To analyze the association of different types of ABL tyrosine point mutations and imatinib resistance to probe the relation between ABL tyrosine point mutations and the prognosis of patients with chronic myeloid leukemia (CML).
  
  
  METHODS
  Nested reverse transcriptasepolym erase chain reaction was performed on samples from 70 patients to amplify the ABL kinase domain. Then, the amplified product was purified and sequenced in both direction. The homologous analysis was performed in combination of clinical data.
  
  
  RESULTS
  The ABL domain point mutations were detected in 32 patients (45.7%) including 16 patients in chronic phase (CP), 6 patients in accelerated phase(AP)and 10 patients in blast phase (BP), which were detected as T315I, E255K, C475Y, Y253H, G321W, G250E, F317L, E258K, F359V, E459K and F311I, respectively. Sokal score with intermediate and high risk and Ph+ chromosome with complex karyotype were important risk factors for ABL domain point mutations. The 5-year overall survival (OS) was not significantly different between the patients with or without ABL domain point mutations (78.1% vs 84.2%, P=0.985), while the 5-year cumulative event-free survival (EFS) of two groups were 34.4% and 68.4% (P=0.034), respectively. The rate of complete cytogenetic response was higher in patients treated with allogenic hematopetic stem cell transplantation (allo-HSCT) compared with patients merely treated with second-generation tyrosine kinase inhibitors or chemotherapeutics (P=0.001).
  
  
  CONCLUSIONS
  Patients with ABL domain point mutations had poor efficacy and prognosis compared to those without ABL domain point mutations. Detection of ABL domain point mutations in CML-CP was helpful for the adjustment of therapeutic options and improvement of prognosis. And allo-HSCT was a more effective therapy for patients with advanced phase.
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Guanlun
authors.initials: G
authors.lastname: Gao
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Na
authors.initials: N
authors.lastname: Xu
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Changxin
authors.initials: C
authors.lastname: Yin
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yajuan
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Libin
authors.initials: L
authors.lastname: Liao
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Cao
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Fanyi
authors.initials: F
authors.lastname: Meng
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001549:Benzamides / Q000627:therapeutic use; D002648:Child; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use; D017354:Point Mutation; D011379:Prognosis; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics*; D011743:Pyrimidines / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016315:Proto-Oncogene Proteins c-abl