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In neuroblastoma (NBL), a clinically heterogeneous and aggressive paediatric malignancy, the prognostic role of PML and its post\u2010translational modifications remains largely unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We investigated the prognostic and predictive significance of PML expression and its site\u2010specific phosphorylation at serine 518 (S\n                      <jats:sup>518<\/jats:sup>\n                      ) in a cohort of 121 NBL patients. Custom\u2010synthesised antibodies and high\u2010resolution tissue microarrays were used to quantitatively profile PML and pPML S\n                      <jats:sup>518<\/jats:sup>\n                      expression via automated immunohistochemistry and digital image analysis. Survival outcomes were assessed using Kaplan\u2010Meier and Cox regression analyses. Mechanistic insights were obtained using reverse\u2011engineered phospho\u2011mutant models enabling selective modulation of S518 phosphorylation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our findings reveal\u00a0a striking inverse relationship between PML abundance and S\n                      <jats:sup>518<\/jats:sup>\n                      phosphorylation, with low PML and high pPML S\n                      <jats:sup>518<\/jats:sup>\n                      strongly associated with advanced disease stage, metastasis, relapse, and therapy resistance. Survival analyses demonstrate that low\u00a0PML\u00a0predicts poor overall survival (OS), progression\u2010free survival (PFS), and relapse\u2010free survival (RFS), while elevated pPML S\n                      <jats:sup>518<\/jats:sup>\n                      correlates with significantly worse outcomes across all endpoints. Multivariate Cox regression confirms both markers as independent predictors of survival. Mechanistically, reverse\u2010engineered phospho\u2010mutant models that enable selective switch\u2010on\/switch\u2010off modulation of S\n                      <jats:sup>518<\/jats:sup>\n                      phosphorylation demonstrated that phosphorylation at this site reduces PML abundance and promotes invasive cellular phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      PML loss and site\u2010specific phosphorylation of PML at S\n                      <jats:sup>518<\/jats:sup>\n                      represent robust prognostic and predictive biomarkers with potential utility in risk stratification. Targeting PML phosphorylation may offer a promising translational strategy to improve therapeutic efficacy in high\u2011risk NBL.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>PML depletion is a defining feature of aggressive neuroblastoma and is associated with advanced stage, metastasis and relapse.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            S\n                            <jats:sup>518<\/jats:sup>\n                            phosphorylation emerges as the dominant post translational trigger committing PML to ubiquitin mediated degradation.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            High pPML S\n                            <jats:sup>518<\/jats:sup>\n                            and low PML form a powerful prognostic axis that independently predicts OS, PFS, and RFS in neuroblastoma.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            PML loss and S\n                            <jats:sup>518<\/jats:sup>\n                            phosphorylation define a molecular framework of heightened cellular plasticity underlying aggressive clinical behavior.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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