The features of FLT3 internal tandem duplication (ITD) in acute myeloid leukemia (AML) patients and impact on prognosis

IntroductionFLT3-ITD is a common genetic aberration in AML, but the prognostic value of its related characteristics remains controversial. This study aimed to re-evaluate the prognostic roles of FLT3-ITD length, insertion site, allelic ratio, and co-mutations.MethodsA retrospective analysis was conducted on 342 non-M3 AML patients with FLT3-ITD mutations (Nov 2021–Feb 2023). FLT3-ITD was detected by targeted next-generation sequencing (tNGS) and capillary electrophoresis (CE). Kaplan-Meier and Cox regression analyses were used to assess factors influencing event-free survival (EFS).ResultsThe tNGS panel used showed high consistency with CE in detecting FLT3-ITD. Median FLT3-ITD insertion length was 42 bp; 72.7% mutations were in the juxtamembrane domain (JMD) , 26.6% in the tyrosine kinase subdomain 1 (TKD1). Kaplan-Meier analysis indicated FLT3-ITD Variant Allele Frequency (VAF) >29.4%, FLT3-ITD length >42 bp, TKD1 localization, and concurrent FLT3-TKD mutations correlated with shorter EFS (all p29.4% (HR: 2.632; 95% CI: 1.328-5.208; p=0.006) and FLT3-ITD/FLT3-TKD co-mutations (HR: 2.591; 95% CI: 1.144-5.882; p=0.022) as independent poor prognostic factors for shorter EFS.ConclusionOur findings identify the higher FLT3-ITD VAF and FLT3-ITD/FLT3-TKD co-mutations as critical independent prognostic markers in FLT3-ITD mutation-positive AML patients.