The mutational spectrum of FLT3 gene in acute lymphoblastic leukemia is different from acute myeloid leukemia

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Abstract

Mutations in FMS-like tyrosine kinase 3 (FLT3) gene occur frequently in acute myeloid leukemia (AML) and are rare in acute lymphoblastic leukemia (ALL). We aimed to analyze the incidence and characteristics of FLT3 mutations in ALL. Amplicon-targeted next-generation sequencing of 58 genes was performed on 1571 patients (AML, n = 829; ALL, n = 742). FLT3 mutations were identified in 5.12% (38/742) of ALL patients. Four types of FLT3 mutations were disclosed, including internal tandem duplication (ITD), tyrosine kinase domain (TKD), juxtamembrane insertion and deletion (JM-INDEL), and juxtamembrane point mutation (JM-PM), which were respectively identified in 1.21, 1.89, 0.67, and 1.89% of patients. The incidence of FLT3-JM-PM (1.89 vs 0.48%, P = 0.009) and the proportion of TKD non-D835 mutations that accounted for the total TKD mutations (57.14 vs 18.18%, P = 0.013) were significantly higher in ALL when compared with AML. FLT3-JM-INDEL were mainly found in B-ALL. In addition, FLT3-JM-INDEL and FLT3-JM-PM were first reported in patients with B-ALL. Patients with FLT3 mutations besides of ITD and/or TKD had a potential response to tyrosine kinase inhibitors. We showed that the mutation spectrum of FLT3 gene in ALL is distinct from AML that will facilitated an in-depth understand of the pathogenesis and provide a guidance for treatment.

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Correspondence to Hongxing Liu.

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