Characteristics and Prognosis of Adult Acute Myeloid Leukemia with Internal Tandem Duplication in the FLT3 Gene

OBJECTIVES: Constitutive activation of the fms-like tyrosine kinase 3 (FLT3) receptor by internal tandem duplication (ITD) of the juxtamembrane region has been described in patients with acute myeloid leukemia. FLT3/ITDs are present in about 20-30% of all acute myeloid leukemia cases. It has been shown that the mutation is correlated with worse prognosis. However, none of the previous studies investigated which FAB subtype is associated with higher percentage of FLT3/ITD, thus the reason for undertaking the current study. METHODS: The prevalence and the potential prognostic impact of FLT3 mutations in 39 acute myeloid leukemia patients were analyzed by genomic polymerase chain reaction. Twelve samples with FLT3/ITDs and 27 acute myeloid leukemia samples without the mutations were compared with respect to clinical prognosis and FAB subtype. Results were correlated with cytogenetic data and the clinical response. RESULTS: FLT3/ITD mutations were found in 31% of patients. FLT3/ITD was associated with similar clinical characteristics and was more prevalent in patients with normal karyotype (83%). Interestingly, half of the FLT3/ITD aberrations were found in patients with FAB M1 (50%), and fewer were found in patients with FAB M2 (8%), M4 (8%), and M5 (8%). Although less frequent in patients with cytogenetic aberrations, FLT3/ITDs were found in 17% of patients with t(15;17). Although the study was powered to 80%, patients with FLT3/ITD mutation did not show shorter complete remission duration or a higher relapse rate. CONCLUSION: The data confirm that FLT3/ITD mutations represent a common alteration in adult acute myeloid leukemia, mainly with normal karyotype (83%) and de novo acute myeloid leukemia (75%), as compared to secondary acute myeloid leukemia (25%) (p<0.001). It also showed that half of the M1-FAB subtype is FLT3/ITD positive. Therefore, FLT3/ITD is a therapeutic target, and thus inhibition of FLT3 tyrosine kinase activity may provide a new approach in the treatment of leukemia carrying these mutations.