N-WASP is downregulated in patients with acute myeloid leukemia (AML) and is associated with poor prognosis.

Acute myeloid leukemia (AML) is a highly lethal hematologic malignancy, and reliable prognostic biomarkers remain urgently needed. We investigated the expression and clinical relevance of the actin cytoskeleton regulator N-WASP in AML. Analysis of TCGA data revealed significantly reduced N-WASP expression in AML compared with normal tissues, and low expression was associated with adverse clinical features, including FAB-M1/M4 subtypes, DNMT3A mutations, and cytogenetic abnormalities such as t(8;21)/RUNX1::RUNX1T1 and del(7q). Patients with low N-WASP expression exhibited shorter overall survival, and multivariate Cox regression identified N-WASP reduction as an independent risk factor, alongside advanced age and FLT3, DNMT3A and TP53 mutations. Co-expression and enrichment analysis highlighted FNIP1, CLIP1, RICTOR and BRAF as N-WASP-associated regulators converging on mTOR signaling. Experimental validation via RT-qPCR and western blotting in AML bone marrow samples and cell lines confirmed the downregulation of N-WASP and key co-expressed genes. Collectively, these results demonstrate that N-WASP is suppressed in AML and is closely associated with disease risk and clinical outcome. N-WASP may serve as a novel prognostic biomarker and potential therapeutic target warranting further investigation.