FLT3 Mutations in Acute Myeloid Leukemia: Unraveling the Molecular Mechanisms and Implications for Targeted Therapies.

Abstract

Acute myeloid leukemia (AML) is a heterogeneous and aggressive form of blood cancer characterized by theuncontrolled proliferation of myeloid precursor cells in the bone marrow. It affects individuals of all ages,with incidence increasing notably in those over 65 years old. Despite advancements in treatment, overallsurvival rates remain unsatisfactory, underscoring the need for a deeper understanding of the disease. Among the various genetic alterations implicated in AML pathogenesis, mutations in the FLT3 (Fms-like tyrosine kinase 3) gene haveemerged as significant contributors to leukemogenesis. The FLT3 ​​​​​gene encodes atype III receptor tyrosine kinase crucial in regulating normal hematopoiesis. Approximately one-third ofAML patients carry FLT3 mutations, making it one of the most frequently mutated genes in the disease. FLT3mutations can be classified into internal tandem duplications (ITDs) and point mutations in the tyrosinekinase domain (TKD).FLT3 mutations are associated with adverse clinical features and are independent prognostic factors for pooroverall survival and decreased remission rates in AML patients. Understanding the molecular mechanisms underlying FLT3 mutations in AML is critical for improving risk stratification, prognosis assessment, and the development of targeted therapies.By reviewing the current literature, this study aims to elucidate the functional consequences of FLT3 mutations in AML pathogenesis, explore the interaction of FLT3 signaling with other oncogenic pathways, and assess the prognostic significance of FLT3 mutations in clinical practice, providing information that can guide future research directions and facilitate the development of more effective therapeutic strategies.