title: Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia: correlation to cytogenetics, FAB subtype, and prognosis in the AMLCG study and usefulness as a marker for the detection of minimal residual disease.
abstract: FLT3 length mutation (FLT3-LM) is a molecular marker potentially useful for the characterization of acute myeloid leukemia (AML). To evaluate the distribution of FLT3-LM within biologic subgroups, we screened 1003 patients with AML at diagnosis for this mutation. FLT3-LM was found in 234 (23.5%) of all patients and thus is the most frequent mutation in AML described so far. Of all positive patients, 165 (70.5%) revealed a normal karyotype. Of the 69 patients with chromosome aberrations, 24 (34.8%) had a t(15;17). The mutation was rare in AML with t(8;21), inv(16) 11q23 rearrangements, and complex karyotypes. FLT3-LM was not distributed equally within different French-American-British (FAB) subtypes and was correlated with a high peripheral blood count in FAB M1, M2, and M4 (P <.0001). In addition, the median age of patients with the mutation was lower (54.9 vs 57.6 years; P =.043), and, at a ratio of 1.36:1 (P =.023), the mutation was more frequent in females than in males. Within the AMLCG study, FLT3-LM was of intermediate prognostic significance. The complete remission rate of 70.3% in patients with FLT3-LM was similar to that (70.4%) in patients without FLT3-LM. Overall survival was not different between patients with or without FLT3-LM. In contrast, patients with FLT3-LM had a significantly shorter event-free survival (7.4 vs 12.6 months; P =.0072) because of a higher relapse rate. Besides the importance of FLT3-LM for biologic and clinical characterization of AML, we show its value as a marker for disease monitoring based on 120 follow-up samples of 34 patients.
authors.affiliation: Department of Internal Medicine III, University of Munich, Germany. susanne.schnittger@med3.med.uni-muenchen.de
authors.forename: Susanne
authors.initials: S
authors.lastname: Schnittger
authors.forename: Claudia
authors.initials: C
authors.lastname: Schoch
authors.forename: Martin
authors.initials: M
authors.lastname: Dugas
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kern
authors.forename: Peter
authors.initials: P
authors.lastname: Staib
authors.forename: Christian
authors.initials: C
authors.lastname: Wuchter
authors.forename: Helmut
authors.initials: H
authors.lastname: Löffler
authors.forename: Cristina Maria
authors.initials: CM
authors.lastname: Sauerland
authors.forename: Hubert
authors.initials: H
authors.lastname: Serve
authors.forename: Thomas
authors.initials: T
authors.lastname: Büchner
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
mesh_terms: D000208:Acute Disease; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D002869:Chromosome Aberrations; D015331:Cohort Studies; D020732:Cytogenetic Analysis; D004252:DNA Mutational Analysis; D005787:Gene Frequency; D006801:Humans; D007951:Leukemia, Myeloid / Q000145:classification / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008875:Middle Aged; D009154:Mutation; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000235:genetics / Q000401:mortality; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D016019:Survival Analysis; D051941:fms-Like Tyrosine Kinase 3
chemical_list: D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins; C497970:FLT3 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3