Ubiquitin-specific protease 34 serves as a novel prognostic biomarker through correlating with immune responses and cell proliferation in acute myeloid leukemia.

Background: Emerging evidence showed that ubiquitin-specific proteases (USPs) are promising therapeutic targets for hematopoietic malignancies. The roles of USP34 on acute myeloid leukemia (AML) pathogenesis remain completely unknown.

Methods: Gene expression and prognostic relevance were analyzed utilizing public AML datasets from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), and validated with the Gene Expression Profiling Interactive Analysis (GEPIA), BloodSpot and the human protein atlas (HPA) databases. Systematical analyses are performed to characterize the immune infiltration and biological function of USP34 in AML. MTS, colony formation and EdU assays were also employed to confirm the effect of USP34 on cell proliferation in AML cells.

Results: USP34 expression was significantly higher in AML compared to its matched normal samples. Higher USP34 expression predicted worse prognosis in AML, and USP34 acted as an independent prognostic predictor for AML patients (HR:1.365, 95%CI:1.032-1.805, p = 0.029). Moreover, the expression of USP34 was associated with several immune cells, including Treg cells, indicating its potential role in modulating immune responses. Finally, functional experiments revealed that USP34 knockdown reduced cell proliferation in Molm-13 and Kasumi cells.

Conclusions: USP34 is an independent prognostic predictor in AML and may contribute to leukemogenesis via intervening immune processes and promoting proliferation.