title: [Analysis of tyrosine kinases gene mutations in core binding factor related acute myeloid leukemia and its clinical significance].
abstract: OBJECTIVE
  To assess the prevalence of several tyrosine kinases (TKs) gene mutations including c-Kit, FLT3 and JAK2 V617F in core binding factor related acute myeloid leukemia (CBF-AML), and analyze their impact on clinical characteristics and prognosis.
  
  
  METHODS
  Mutations of c-Kit, FLT3-ITD and FLT3-TKD were detected by genomic DNA PCR and sequencing, and JAK2 V617F mutation screening by allele-specific PCR in 58 newly diagnosed CBF-AML patients [28 AML with inv(16) and 30 with t(8;21)], and analyze the patients clinical characteristics and prognoses.
  
  
  RESULTS
  c-Kit aberrations were detected in 32.8% cases, including 6 cases mutated in exon 8 (mutKIT8) and 13 mutated in exon 17 (mutKIT17). MutKIT8 was more prominent in inv(16) than in t(8;21) patients (21.4% vs 0, P = 0.009). Only 2 cases had FLT3-ITD and 7 (12.1%) FLT3-TKD mutations. The result of JAK2 V617F mutation screenings in these CBF-AML patients was negative. The frequency of receptor tyrosine kinases(RTK) mutations was 46.6% and only one case had two kinds of missense mutations (mutKIT8 & TKD(+)). Median age of onset was higher for mutKIT17 than for wide-type c-Kit (wtKIT) patients (55 vs 31, P = 0.003). c-Kit mutations were significantly associated with decreased overall survival (OS) and continuous complete remission (CCR) rates (P = 0.053, and 0.048 respectively), and so did more for exon17 mutated patients reduced (P = 0.005, and 0.013 respectively). FLT3-TKD mutation showed no effects on prognosis of CBF-AML patients.
  
  
  CONCLUSIONS
  RTK mutations are common in patients with CBF-AML. c-Kit mutations frequently and JAK2V617F mutation rarely appear in CBF-AML. c-Kit mutations, especially mutKIT17 confers higher relapse risk and poorer prognosis.
authors.affiliation: Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Man
authors.initials: M
authors.lastname: Qiao
authors.forename: Wei-yang
authors.initials: WY
authors.lastname: Li
authors.forename: Ai-ning
authors.initials: AN
authors.lastname: Sun
authors.forename: Su-ning
authors.initials: SN
authors.lastname: Chen
authors.forename: Jian-ying
authors.initials: JY
authors.lastname: Liang
authors.forename: Zi-xuan
authors.initials: ZX
authors.lastname: Ding
authors.forename: Yu-feng
authors.initials: YF
authors.lastname: Feng
authors.forename: De-pei
authors.initials: DP
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D050660:Core Binding Factors; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
chemical_list: D050660:Core Binding Factors; C497970:FLT3 protein, human; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; D051941:fms-Like Tyrosine Kinase 3; C507924:JAK2 protein, human; D053614:Janus Kinase 2