Proteomics in Acute Myeloid Leukemia: Current Applications in Precision Medicine and Targeted Immunotherapy

Acute myeloid leukemia (AML) is a heterogeneous and aggressive malignancy with limited therapeutic options and high relapse rates. Despite advances in genomic profiling, many genetic aberrations remain untargetable, and current risk stratification models often fail to predict treatment responses. Proteomics offers a complementary approach by directly measuring protein abundance, post-translational modifications, and protein–protein interactions, providing mechanistic insights into drug resistance, disease progression, and therapeutic vulnerabilities. In this review, we explore the emerging role of proteomics in AML, focusing on its application in biomarker discovery, prediction of drug responses, and identification of novel therapeutic targets. Special attention is given to antigen discovery for immunotherapy, where surface and immunopeptidomics enable the identification of AML-specific antigens and neoepitopes. These insights are critical for the development of antigen-targeted therapies, including chimeric antigen receptor (CAR) and T cell receptor (TCR)-based immunotherapies. Integrating proteomics into a multiomics framework could provide actionable insights for guiding precision medicine and improving AML outcomes.