title: Screening for hotspot mutations in PI3K, JAK2, FLT3 and NPM1 in patients with myelodysplastic syndromes.
abstract: BACKGROUND
  Myelodysplastic syndromes encompass a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, refractory cytopenia and a tendency to progress toward acute myeloid leukemia. The accumulation of genetic alterations is closely associated with the progression of myelodysplastic syndromes toward acute myeloid leukemia.
  
  
  OBJECTIVE
  To investigate the presence of mutations in the points most frequent for mutations (hotspot mutations) in phosphatidylinositol-3-kinase (PI3K), Janus kinase 2 (JAK2), FMS-like tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1), which are involved in leukemia and other cancers, in a population of Brazilian MDS patients.
  
  
  METHODS
  Fifty-one myelodysplastic syndromes patients were included in the study. According to French-American-British classification, the patients were distributed as follows: 31 with refractory anemia, 8 with refractory anemia with ringed sideroblasts, 7 with refractory anemia with excess blasts, 3 with refractory anemia with excess blasts in transformation and 2 with chronic myelomonocytic leukemia. Bone marrow samples were obtained and screened for the presence of hotspot mutations using analysis based on amplification with the polymerase chain reaction, sequencing, fragment size polymorphisms or restriction enzyme digestion. All patients were screened for mutations at the time of diagnosis, and 5 patients were also screened at the time of disease progression.
  
  
  RESULTS
  These results show that hotspot mutations in the PI3K, JAK2, FLT3 and NPM1 genes are not common in MDS patients; nevertheless, JAK2 mutations may be present in myelodysplasia during disease progression.
  
  
  CONCLUSIONS
  These results show that hotspot mutations in the PI3K, JAK2, FLT3 and NPM1 genes are not common in MDS patients; nevertheless, JAK2 mutations may be present in myelodysplasia during disease progression.
authors.affiliation: Hematology and Hemotherapy Center, National Institute of Blood, University of Campinas, São Paulo, Brazil.
authors.forename: João Agostinho
authors.initials: JA
authors.lastname: Machado-Neto
authors.forename: Fabiola
authors.initials: F
authors.lastname: Traina
authors.forename: Mariana
authors.initials: M
authors.lastname: Lazarini
authors.forename: Paula de Melo
authors.initials: Pde M
authors.lastname: Campos
authors.forename: Katia Borgia Barbosa
authors.initials: KB
authors.lastname: Pagnano
authors.forename: Irene
authors.initials: I
authors.lastname: Lorand-Metze
authors.forename: Fernando Ferreira
authors.initials: FF
authors.lastname: Costa
authors.forename: Sara T Olalla
authors.initials: ST
authors.lastname: Saad
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005820:Genetic Testing; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D000090243:Nucleophosmin; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics*; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D000090243:Nucleophosmin; D058539:Phosphatidylinositol 3-Kinase; D051941:fms-Like Tyrosine Kinase 3; D053614:Janus Kinase 2