title: [Detection of point mutation at second tyrosine kinase domain of FLT3 gene in acute myeloid leukemia].
abstract: OBJECTIVE
  To evaluate the prevalence of a novel FLT3 activating mutation in tyrosine kinase domain (TDK) in acute leukemia patients and its clinical implication.
  
  
  METHODS
  Genomic DNA from bone marrow mononuclear cells of 143 cases of acute myeloid leukemia (AML), 25 acute lymphocytic leukemia (ALL), 2 acute hybrid leukemia (AHL), 17 myelodysplastic syndromes (MDS) and 7 chronic myelogenous leukemia in blast crisis (CML-BC) was screened by polymerase chain reaction (PCR) and gel electrophoresis for FLT3-TKD point mutations.
  
  
  RESULTS
  Among AML patients, FLT3-TKD point mutation (FLT3-TKD(+)) rate was 6.3% (9/143), an incidence significantly lower than that of internal tandem duplication (ITD) mutation (37/143, 25.9%, P < 0.01). According to the FAB classification, FLT3-TKD point mutation was found in 3/53 of M(2), 3/40 of M(3), 2/23 of M(5) and 1/2 of M(6) subtypes. Two patients showed both ITD and TKD mutations. No FLT3-TDK mutation was found in 25 ALL, 2 AHL, 17 MDS and 7 CML-BC patients. Sequence analysis showed that one of the mutations occurred at codon 835 of FLT3. The substitution of the first nucleotide T for G of D835, resulted in D835Y, a missense mutation. The presence of TKD mutations was related neither to age, sex, nor to WBC counts, the marrow blast percentages, and CR rates for induction therapy. CONCLUSION The incidence of FLT3-TKD(+) is significantly lower than that of ITD mutation. FLT3-TKD mutations may occur alone or together with ITD mutation. In contrast to FLT3-ITD mutation, TKD mutations were not associated with leukocytosis or low complete remission rate.
authors.affiliation: State Key Laboratory of Experimental Hematology, Department of Clinical Hematology, Institute of Hematology and Blood Diseases Hospital, CAMS and PUMC, Tianjin 300020, China.
authors.forename: Li-hong
authors.initials: LH
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Chun-lin
authors.initials: CL
authors.lastname: Zhou
authors.forename: Sen
authors.initials: S
authors.lastname: Chen
authors.forename: Xin-wei
authors.initials: XW
authors.lastname: Zhang
authors.forename: Hai-yan
authors.initials: HY
authors.lastname: Xing
authors.forename: Jian-xiang
authors.initials: JX
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D051941:fms-Like Tyrosine Kinase 3