Diagnostic and Prognostic Significance of miR-155, miR-181, miR-221, miR-222, and miR-223 Expression in Myelodysplastic Syndromes and Acute Myeloid Leukemia

<b>Background:</b> Myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML) are clonal hematological disorders that share molecular origins but present with distinct clinical features. MicroRNAs (miRNAs) are key post-transcriptional regulators, and their altered expression may reflect biological shifts contributing to disease progression. <b>Methods:</b> Expression levels of miR-155, miR-181, miR-221, miR-222, and miR-223 were analyzed by RT-qPCR in bone marrow samples from 37 MDS patients, 20 AML patients, and 7 controls. Group comparisons were performed using ANOVA (with Benjamini-Hochberg correction) and Tukey post hoc testing. Diagnostic performance and network behavior were evaluated using ROC analysis, Pearson correlation matrices, and principal component analysis (PCA). <b>Results:</b> miR-155, miR-181, and miR-223 were upregulated in AML, whereas miR-221 and miR-222 were downregulated. miR-222 showed the highest diagnostic accuracy (AUC ~0.87 for both AML vs. control and MDS vs. control). Its expression was significantly higher in high IPSS-R MDS cases (<i>p</i> = 0.046), with a similar upward tendency for miR-221 (<i>p</i> = 0.054). Progressive loss of coordinated miRNA expression was observed from controls to MDS and AML. PCA supported these findings by showing separation mainly driven by miR-222 and miR-155. <b>Conclusions:</b> Combined miRNA profiling highlights miR-222 and, to a lesser extent miR-155, as consistent indicators of myeloid disease transformation. While further validation in larger and genetically stratified cohorts is warranted, these findings support the potential contribution of miRNA signatures to diagnostic evaluation and risk stratification in MDS and AML, in line with precision hematology approaches.