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

• Published in: Blood 2002-07, Vol.100 (1), p.59-66
• Main Authors: Schnittger, Susanne, Schoch, Claudia, Dugas, Martin, Kern, Wolfgang, Staib, Peter, Wuchter, Christian, Löffler, Helmut, Sauerland, Cristina Maria, Serve, Hubert, Büchner, Thomas, Haferlach, Torsten, Hiddemann, Wolfgang
• Format: Article
• Language: English
• Subjects: Acute Disease; Biological and medical sciences; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Chromosome Aberrations; Cohort Studies; Cytogenetic Analysis; DNA Mutational Analysis; fms-Like Tyrosine Kinase 3; Gene Frequency; Hematologic and hematopoietic diseases; Humans; Leukemia, Myeloid - classification; Leukemia, Myeloid - diagnosis; Leukemia, Myeloid - genetics; Leukemia, Myeloid - mortality; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Middle Aged; Mutation; Neoplasm, Residual - diagnosis; Neoplasm, Residual - genetics; Neoplasm, Residual - mortality; Prognosis; Proto-Oncogene Proteins - genetics; Receptor Protein-Tyrosine Kinases - genetics; Survival Analysis
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V100.1.59

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.