Targeting FMS-Like Tyrosine Kinase 3 (FLT3) in Acute Myeloid Leukemia: Novel Molecular Approaches and Therapeutic Challenges

Acute myeloid leukemia (AML), a heterogeneous hematologic malignancy, has generally a poor prognosis despite the recent advancements in diagnostics and treatment. Genetic instability, particularly mutations in the FMS-like tyrosine kinase 3 (FLT3) gene, is associated with severe outcomes. Approximately 30% of AML patients harbor FLT3 mutations, which have been linked to higher relapse and reduced survival rates. Traditional AML treatments employ cytarabine and anthracyclines drugs. Furthermore, the development of FLT3 inhibitors has significantly improved therapy for FLT3-mutated AML patients. For example, the introduction of midostaurin, the first FLT3 inhibitor, improved patient outcomes. However, resistant AML cell clones continue to pose a challenge to the success of AML treatment.2This review discusses FLT3 kinase, mutations, and role in AML pathogenesis. It explores the molecular mechanisms of FLT3 activation, signaling pathways, and the structure and function of the FLT3 receptor. Current and emerging therapeutic approaches are presented, while highlighting the latest FLT3 inhibitors in clinical use, and strategies to overcome drug resistance. Future directions, including personalized therapies and novel drug designs, are examined to provide updated insights into FLT3-targeted treatments. This comprehensive review aims to guide clinicians and researchers in the development of innovative therapies to improve AML patient outcomes.