en AI in Medicine پژوهشي Original Article <div style="text-align: justify;"><span style="font-size:14px;"><span style="line-height:2;"><span style="font-family:Times New Roman;"><strong>Background: </strong>Acute myeloid leukemia (AML) has poor long-term survival, necessitating robust prognostic biomarkers. While conventional markers focus on cytogenetics and mutations, immune-extracellular genes suitable for liquid biopsy remain understudied.<br> <strong>Methods:</strong> RNA-sequencing data from 200 AML patients were analyzed from The Cancer Genome Atlas (TCGA). Univariate Cox regression identified survival-associated genes. Gene Ontology enrichment analysis selected immune and extracellular genes, with Kaplan-Meier analysis validating prognostic significance. REACTOME pathway enrichment revealed biological mechanisms. External validation used GEPIA2.<br> <strong>Results: </strong>Cox regression identified 201 survival-associated genes (p<0.05): 149 favorable prognosis (HR<1) and 52 poor prognosis (HR>1). Gene Ontology enrichment revealed 29 immune-associated and 9 extracellular genes, with 5 overlapping candidates. Kaplan-Meier analysis confirmed four genes; EPHA10, CD160, BTN2A2, and KLRK1 as significant protective prognostic markers (p<0.05, HR<1). REACTOME analysis highlighted immune signaling pathways including adaptive immune response, natural killer cell-mediated cytotoxicity, and cell surface interactions. External validation demonstrated differential expression in AML versus normal tissues.<br> <strong>Conclusion:</strong> This study identified EPHA10, CD160, BTN2A2, and KLRK1 as novel immune-extracellular prognostic biomarkers in AML. These genes represent promising candidates for liquid biopsy applications and personalized immunotherapy strategies, offering new perspectives for monitoring immune surveillance and overcoming AML immune evasion.</span></span></span></div> Acute myeloid leukemia, Biomarkers, Immune microenvironment, Extracellular genes, Prognosis, TCGA 40 48 http://ijbc.ir/browse.php?a_code=A-10-2180-3&slc_lang=en&sid=1 Nikoo Saeedi 100319475328460013144 100319475328460013144 Yes Student Research Committee, Islamic Azad University, Mashhad Branch, Mashhad, Iran. Ghazaleh Khalili Tanha 100319475328460013145 100319475328460013145 No Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Amir Ali Judaki magh2022@gmail.com 100319475328460013146 100319475328460013146 No Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Elham Nazari Elham.nazari@sbmu.ac.ir 100319475328460013147 100319475328460013147 No Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.