title: FMS-Like Tyrosine Kinase 3 (FLT3) and Nucleophosmin 1 (NPM1) in Iranian Adult Acute Myeloid Leukemia Patients with Normal Karyotypes: Mutation Status and Clinical and Laboratory Characteristics.
abstract: OBJECTIVE
  In this study, we evaluated the frequency of FMS-like tyrosine kinase 3 (FLT3-ITD and FLT3-TKD) and nucleophosmin (NPM1) mutations in Iranian patients with cytogenetically normal acute myeloid leukemia (CN-AML). The clinical and laboratory characteristics were compared between wild-type and mutant cases.
  
  
  METHODS
  Seventy newly diagnosed de novo AML patients were recruited at the time of diagnosis prior to chemotherapy; among them, 54 had CN-AML. For detecting mutations, the FLT3 and NPM1 genes were amplified by the polymerase chain reaction method, followed by direct sequencing.
  
  
  RESULTS
  Our results showed that the frequencies of FLT3-ITD, FLT3-TKD, and NPM1 mutations in CN-AML patients were 25.9%, 5.9%, and 20.8%, respectively. The most frequent NPM1 mutation type was the type A mutation. The FLT3-ITD mutation was seen more frequently in non-M3 patients compared with M3 patients. No mutation was observed in either the FLT3-TKD or the NPM1 gene in patients in the M3 French-American-British group. There was no significant association between the presence of FLT3-ITD and NPM1 mutations in CN-AML patients (p>0.05). The frequency of FLT3-ITD, FLT3-TKD, and NPM1 mutation was higher in CN-AML patients in comparison with AML patients with cytogenetic aberrations, although the differences were not statistically significant (p>0.05). There were no significant differences in mean white blood cell and platelet counts, serum hemoglobin levels, and bone marrow blast percentages between patients with wild-type and mutant FLT3-ITD and NPM1 genes (p>0.05). No difference was observed in the frequency of FLT3-ITD or NPM1 mutation regarding age or sex (p>0.05).
  
  
  CONCLUSIONS
  Given the high stability of NPM1 during the disease course, it can be used in combination with FLT3 as well as other known genetic markers to monitor patients, especially for minimal residual disease detection.
authors.affiliation: Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Narges
authors.initials: N
authors.lastname: Rezaei
authors.affiliation: Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Nargess
authors.initials: N
authors.lastname: Arandi
authors.affiliation: Department of Pathology, Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Behnaz
authors.initials: B
authors.lastname: Valibeigi
authors.affiliation: Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Sezaneh
authors.initials: S
authors.lastname: Haghpanah
authors.affiliation: Namazi Hospital, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Khansalar
authors.affiliation: Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Mani
authors.initials: M
authors.lastname: Ramzi
mesh_terms: D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D007492:Iran / Q000453:epidemiology; D059785:Karyotype; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3
keywords: Acute myeloid leukemia; FLT3 NPM1.; Gene mutation