Neutrophil-related genes predict prognosis and contribute to immunosuppression in acute myeloid leukemia

Neutrophils, the predominant myeloid cells in human blood, have been implicated as pivotal contributors to cancer development. However, the relationship between neutrophils and acute myeloid leukemia (AML) prognosis remains unclear due to their great plasticity and diversity. In this study, we conducted a comprehensive analysis of gene expression data and clinical records from AML patients sourced from TCGA, GEO, and OHSU databases. We established a neutrophil-based prognostic model incorporating five neutrophil-related genes (CSF3R、BRAF、FFAR2、CD300A and CD37) and the predictive value of the model was validated in both internal and external validation cohorts. Univariate and Multivariate Cox regression analyses further demonstrated that the model remained an independent prognostic factor for overall survival, and a nomogram was constructed to facilitate its clinical application. Notably, CD37 was identified as a crucial neutrophil-related gene associated with adverse AML prognosis. Elevated CD37 expression was indicative of dysregulated cell proliferation, immunosuppressive tumor microenvironment and T cell dysfunction. Overexpression of CD37 was also correlated with increased expression of PD1, CTLA4, CD86, and LAG3. Furthermore, CD37 could serve as a valuable predictor for immunotherapy and represents a druggable target in AML. In summary, our study advances a novel prognostic model based on neutrophil-related gene expression, with CD37 emerging as a promising biomarker for anti-leukemic response prediction. This insight holds promise for personalized prognosis estimation and informed clinical decision-making in AML management.