The aim of this study was to evaluate the expression ofUSP7,USP15,UBE2O, andUBE2Tgenes in Myelodysplastic neoplasm (MDS) to identify possible targets of ubiquitination and deubiquitination in MDS pathobiology. To achieve this, eight datasets from the Gene Expression Omnibus (GEO) database were integrated, and the expression relationship of these genes was analyzed in 1092 MDS patients and healthy controls. Our results showed thatUBE2O,UBE2T, andUSP7were upregulated in MDS patients compared with healthy individuals, but only in mononucleated cells collected from bone marrow samples (p< 0.001). In contrast, only theUSP15gene showed a downregulated expression compared with healthy individuals (p= 0.03). Additionally, the upregulation ofUBE2Texpression was identified in MDS patients with chromosomal abnormalities compared with patients with normal karyotypes (p= 0.0321), and the downregulation ofUBE2Texpression was associated with MDS hypoplastic patients (p= 0.033). Finally, theUSP7andUSP15genes were strongly correlated with MDS (r = 0.82; r2 = 0.67;p< 0.0001). These findings suggest that the differential expression of theUSP15-USP7axis andUBE2Tmay play an important role in controlling genomic instability and the chromosomal abnormalities that are a striking characteristic of MDS.