Incidence and prognostic value of FLT3 internal tandem duplication and D835 mutations in acute myeloid leukemia

Abstract

BACKGROUND AND OBJECTIVES: Cytogenetics is the most important prognostic factor in acute myeloid leukemia (AML). However, a high proportion of patients show normal or intermediate-risk karyotypes. In these patients, other determinants could help to identify those with a higher risk of relapse. Recently, internal tandem duplications (ITD) and D835 mutations in FLT3 tyrosine kinase receptor have been shown to confer a bad prognosis in AML. DESIGN AND METHODS: We analyzed the incidence of these mutations in a total of 208 patients of different AML subsets and their prognostic relevance in non-promyelocytic de novo AML. RESULTS: FLT3 mutations were detected in 24% of de novo AML, 42% of acute promyelocytic leukemia (APL) and 17% of secondary AML. Four patients showed both ITD and D835 mutations. Ninety-four per cent of the patients with FLT3 alterations were classified into the intermediate-risk group. There was no association between the presence of FLT3 alterations and response to induction while the alterations were associated with a worse disease-free survival and event-free survival in both the overall and intermediate-risk patients. INTERPRETATION AND CONCLUSIONS: Our data confirm that any of the mutations in FLT3 confer a bad prognosis in AML. Because of the high prevalence of these mutations within the intermediate-risk group, their detection could be useful to identify patients with a poor prognosis.