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

Acute myeloid leukemia (AML) is a heterogeneous and aggressive form of blood cancer characterized by the uncontrolled 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, overall survival 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 (Fms-like tyrosine kinase 3) gene have emerged as significant contributors to leukemogenesis. The ​​​​​gene encodes a type III receptor tyrosine kinase crucial in regulating normal hematopoiesis. Approximately one-third of AML patients carry mutations, making it one of the most frequently mutated genes in the disease. mutations can be classified into internal tandem duplications (ITDs) and point mutations in the tyrosine kinase domain (TKD).  mutations are associated with adverse clinical features and are independent prognostic factors for poor overall survival and decreased remission rates in AML patients. Understanding the molecular mechanisms underlying 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 mutations in AML pathogenesis, explore the interaction of signaling with other oncogenic pathways, and assess the prognostic significance of mutations in clinical practice, providing information that can guide future research directions and facilitate the development of more effective therapeutic strategies.