WT1 as a Biomarker in Myelodysplastic Neoplasms: Clinical Correlations and Preliminary Data from an Iranian Cohort

Background: Although Wilms' tumor 1 (WT1) mRNA overexpression is frequently observed in myelodysplastic neoplasms (MDS), its clinical and molecular significance remains incompletely defined across diverse populations; this study is the first to evaluate WT1 expression in Iranian patients with MDS. Materials and Methods: WT1 expression was assessed in 58 MDS patients using an ELN-certified quantitative RT-PCR assay. Associations with clinical subtype, hematologic features, cytogenetic profiles, and molecular mutations were analyzed. Survival outcomes were evaluated using Kaplan-Meier and Cox regression analyses. Results: WT1 overexpression was detected in 79.3% of patients and was significantly associated with advanced subtypes (MDS-EB1/EB2) and higher IPSS-R risk groups. Elevated WT1 levels correlated with an increased bone marrow (BM) blast percentage (P < 0.01). Although cytogenetic abnormalities were more frequent in patients with WT1 overexpression, the association did not reach statistical significance. No significant correlations were observed with peripheral blood (PB) cytopenias or mutations in RNA splicing genes. Importantly, WT1 overexpression was associated with shorter overall survival (OS) and progression-free survival (PFS). However, in multivariate analysis, ≥10% BM blasts and an abnormal karyotype remained independent predictors of poor outcome, whereas WT1 overexpression itself was not independently prognostic. Conclusion: WT1 overexpression in MDS is associated with advanced disease features and poorer survival, though it is not an independent prognostic value. Its measurement may complement existing risk stratification, particularly in resource-limited settings.