Collectively, while direct functional experiments in MDS are currently lacking, our data, combined with insights from other cancers, strongly support the hypothesis that PIWIL2 upregulation contributes to MDS pathogenesis through multiple interconnected pathways and that its upregulation in HR-MDS could serve not only as a prognostic predictor but also as a novel approach for personalized therapy of MDS in the future. This evidence concerns the gene PIWIL2 and cancer.