Analysis of FLT3-ITD and FLT3 TKD (D835) Mutations in 506 Adult Colombian Patients with De Novo AML Diagnosed Between February 2019 and June 2022

Abstract

Introduction: The most common genetic alteration in adult patients with de novo AML is the presence of FLT3-ITD or FLT3-TKD (D835) mutations. These variants are an adverse prognostic factor in AML patients. Since 2017, the FDA has approved a TKI inhibitor for patients testing positive for this variant. Materials and Methods: With prior informed consent, we analyzed a total of 506 samples obtained between February 2019 and June 2022 from adult patients with de novo AML using PCR and capillary electrophoresis. Of the patients, 52.3% were male, and 47.8% were female. Results: Out of the 506 processed samples, 105 were positive for FLT3 mutation (20.75%), 71 for FLT3-ITD (67.6%), and 34 for FLT3-TKD (D835) (32.4%). Two samples showed simultaneous mutations for FLT3-ITD and FLT3-TKD (D835). Of the 105 positive samples, 61 (58.1%) had an allelic ratio greater than 0.5 (range 0.5 - 3.86), and 45 samples (42.9%) had an allelic ratio less than 0.5 (range 0.03 - 0.49).

Conclusions: We have implemented a rapid test for the diagnosis of FLT3-ITD and FLT3-TKD (D835) mutations in adult patients with de novo AML. The frequency of these pathogenic variants was 20.75%, which is consistent with results observed in other cohorts worldwide. These findings open the door for AML patients with FLT3 mutations to benefit from targeted therapies.