Dynamics of FLT3 mutations in acute myeloid leukemia: A systematic review and meta-analysis of shifts between diagnosis and relapsed/refractory disease

Abstract

Acute myeloid leukemia (AML) is a hematologic malignancy with a generally poor prognosis. Technological advances in molecular diagnosis have identified genetic alterations driving AML pathogenesis, among which FMS-like tyrosine kinase 3 (FLT3) mutations are significant. These mutations hold prognostic value and are increasingly recognized as potential markers for disease monitoring. This systematic review and meta-analysis aimed to assess the prevalence of changes in FLT3 mutational status in adult patients with relapsed or refractory AML compared to their status at initial diagnosis. A relevant proportion of patients who were FLT3-wildtype at diagnosis were found to be FLT3-mutated on relapse, emphasizing the importance of continuous mutation monitoring. Subgroup analyses were also performed, and mutation shift rates were reported across both FLT3 internal tandem duplication and tyrosine kinase domain subtypes. These findings illustrate the genetic evolution of leukemic clones and support the need for tailored therapeutic approaches based on the mutational profile at different disease stages. This study further highlights the diagnostic and clinical utility of routine molecular reassessment and offers practical recommendations for integrating FLT3 retesting into standard AML management.

Keywords

Acute myeloid leukemia / FMS-like tyrosine kinase 3 mutation / FMS-like tyrosine kinase 3 / Molecular biology

Funding

None.

Conflict of interest

The authors declare they have no competing interests.

References

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