Metabolic Signature of FLT3-Mutated AML: Clinical and Therapeutic Implications

Acute Myeloid Leukemia (AML) is a genetically and clinically heterogeneous malignancy marked by poor prognosis and limited therapeutic options, especially in older patients. While conventional treatments such as the “7 + 3” chemotherapy regimen and allogeneic stem cell transplantation remain standard care options, the advent of next-generation sequencing (NGS) has transformed our understanding of AML’s molecular complexity. Among the emerging hallmarks of AML, metabolic reprogramming has gained increasing attention for its role in supporting leukemic cell proliferation, survival, and therapy resistance. Distinct AML subtypes—shaped by specific genetic alterations, including FLT3, NPM1, and IDH mutations—exhibit unique metabolic phenotypes that reflect their underlying molecular landscapes. Notably, FLT3-ITD mutations are associated with enhanced reactive oxygen species (ROS) production and altered energy metabolism, contributing to disease aggressiveness and poor clinical outcomes. This review highlights the interplay between metabolic plasticity and genetic heterogeneity in AML, with a particular focus on FLT3-driven metabolic rewiring. We discuss recent insights into how these metabolic dependencies may be exploited therapeutically, offering a rationale for the development of metabolism-targeted strategies in the treatment of FLT3-mutated AML.