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

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.