title: Prognostic value of FLT3 mutations in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy.
abstract: BACKGROUND
  Fms-like tyrosine kinase-3 (FLT3) gene mutations are frequent in acute promyelocytic leukemia but their prognostic value is not well established.
  
  
  METHODS
  We evaluated FLT3-internal tandem duplication and FLT3-D835 mutations in patients treated with all-trans retinoic acid and anthracycline-based chemotherapy enrolled in two subsequent trials of the Programa de Estudio y Tratamiento de las Hemopatías Malignas (PETHEMA) and Hemato-Oncologie voor Volwassenen Nederland (HOVON) groups between 1996 and 2005.
  
  
  RESULTS
  FLT3-internal tandem duplication and FLT3-D835 mutation status was available for 306 (41%) and 213 (29%) patients, respectively. Sixty-eight (22%) and 20 (9%) patients had internal tandem duplication and D835 mutations, respectively. Internal tandem duplication was correlated with higher white blood cell and blast counts, lactate dehydrogenase, relapse-risk score, fever, hemorrhage, coagulopathy, BCR3 isoform, M3 variant subtype, and expression of CD2, CD34, human leukocyte antigen-DR, and CD11b surface antigens. The FLT3-D835 mutation was not significantly associated with any clinical or biological characteristic. Univariate analysis showed higher relapse and lower survival rates in patients with a FLT3-internal tandem duplication, while no impact was observed in relation to FLT3-D835. The prognostic value of the FLT3-internal tandem duplication was not retained in the multivariate analysis.
  
  
  CONCLUSIONS
  FLT3-internal tandem duplication mutations are associated with several hematologic features in acute promyelocytic leukemia, in particular with high white blood cell counts, but we were unable to demonstrate an independent prognostic value in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based regimens.
authors.affiliation: Hospital Universitario La Fe, Valencia, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Barragán
authors.forename: Pau
authors.initials: P
authors.lastname: Montesinos
authors.forename: Mireia
authors.initials: M
authors.lastname: Camos
authors.forename: Marcos
authors.initials: M
authors.lastname: González
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Calasanz
authors.forename: José
authors.initials: J
authors.lastname: Román-Gómez
authors.forename: Maria T
authors.initials: MT
authors.lastname: Gómez-Casares
authors.forename: Rosa
authors.initials: R
authors.lastname: Ayala
authors.forename: Javier
authors.initials: J
authors.lastname: López
authors.forename: Óscar
authors.initials: Ó
authors.lastname: Fuster
authors.forename: Dolors
authors.initials: D
authors.lastname: Colomer
authors.forename: Carmen
authors.initials: C
authors.lastname: Chillón
authors.forename: María J
authors.initials: MJ
authors.lastname: Larrayoz
authors.forename: Pedro
authors.initials: P
authors.lastname: Sánchez-Godoy
authors.forename: José
authors.initials: J
authors.lastname: González-Campos
authors.forename: Félix
authors.initials: F
authors.lastname: Manso
authors.forename: Maria L
authors.initials: ML
authors.lastname: Amador
authors.forename: Edo
authors.initials: E
authors.lastname: Vellenga
authors.forename: Bob
authors.initials: B
authors.lastname: Lowenberg
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sanz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002648:Child; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome; D014212:Tretinoin / Q000627:therapeutic use*; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D014212:Tretinoin; D051941:fms-Like Tyrosine Kinase 3