Objective To investigate the heterogeneity of FLT3 mutations and the consequences of co-occurring mutations on the clinical features and prognosis of patients with acute myeloid leukemia (AML).

Methods We retrospectively analyzed the clinical characteristics of 80 patients with AML who carried FLT3 mutations, as detected by genetic testing, and were treated in The First Hospital of Lanzhou University from October 2017 to March 2024. An analysis was performed to evaluate the impact of FLT3 mutation frequency, insertion length of base pairs, insertion site, and co-occurring mutations on survival outcomes.

Results  The variant allele frequency (VAF) of FLT3-ITD mutations was correlated with leukocyte counts and lactate dehydrogenase levels in patients with de novo AML. There was an association between the insertion site and the length of the base-pair insertion. Patients with AML who also had a VAF of FLT3-ITD mutations greater than or equal to 0.38 exhibit reduced overall survival (OS), whereas the length of base pair insertion, insertion site, and number of mutations did not correlate with OS. Patients with non-classical FLT3 mutations demonstrated a significantly longer OS than did those with FLT3-ITD mutations. The co-occurrence of FLT3-ITD, NPM1, and DNMT3A mutations was associated with markedly reduced OS. The use of FLT3 inhibitors and allogeneic hematopoietic stem cell transplantation (allo-HSCT) can improve the prognosis of patients with FLT3-ITD mutations.

Conclusions  FLT3 mutational heterogeneity correlates with the clinical characteristics and outcomes of patients with AML. Non-classical FLT3 and FLT3-TKD mutations are associated with superior prognosis. Patients with a VAF of 0.38 or higher have a poorer prognosis, but the use of FLT3 inhibitors can improve their prognosis. Patients with triple mutations have poor prognosis.