Immunophenotypic findings in acute myeloid leukemia with FLT3 internal tandem duplication

Background and Objectives. The biological characteristics and prognostic significance of the internal tandem duplication of the FLT3 (FLT3/ITD) were investigated in a series of de novo acute myeloid leukemia (AML) patients. One hundred and fifty-six adult patients with AML were included in the study. FLT3/ITD was detected in 41 (26%) patients (FLT3/ITD+). Design and Methods. The main differences observed between the groups with and without FLT3/ITD: a higher leukocyte count, a raised percentage of a normal karyotype and a more frequent M5 FAB diagnosis in the FLT3/ITD+ patients. As regards the immunophenotypic characteristics the FLT3/ITD+ group very often expressed monocytic markers (CD36 and CD11b) and less commonly immature markers (CD34 and CD117). A promyelocytic-like immunophenotype pattern was also detected in a minority of these patients (4/36). Results. The FLT3/ITD+ patients had a shorter overall survival. a shorter event-free survival and a higher probability of relapse. Minimal residual disease (MRD) was investigated in the FLT3/ITD+ patients using flow cytometry. This technique had a sensitivity of 62% and a specificity of 83% in relapse prediction. Minimal residual disease analysis was hampered by the low number of patients with detectable aberrant immunophenotype. Interpretation and Conclusions. A high frequency of changes in the phenotype and/or genotype pattern between diagnosis and relapse was detected (5/6). FLT3/ITD is a frequent molecular lesion in de novo adult AML and seems to be associated with momnocytic differentaition, a high leukocyte count and a poor prognosis. Immunophenotype and genotype patterns observed at relapse suggest that the FLT3/ITD+ blasts may be genetically unstable and prone to clonal evolution. FLT3/ITD may not be a suitable target for minimal residual disease studies. (C) 2003, Ferrata Storti Foundation.