The deubiquitinase USP1 promotes the progression of AML by stabilizing ID1 [RNAseq_AML_shUSP1]

Acute myeloid leukemia (AML) represents a clonal malignant disorder affecting the hematopoietic system, predominantly featuring abnormal clonal proliferation of myeloid precursor cells and linked to unfavorable prognosis. This investigation seeks to improve clinical outcomes through examing the mechanistic role ubiquitin-specific protease 1 (USP1) in AML. Data analysis from The Cancer Genome Atlas (TCGA) and TARGET databases demonstrated that USP1 exhibits high expression in AML, where increased show positive correlation with poor prognostic outcomes. In vitro studies using short hairpin RNA (shRNA) for USP1 knockdown showed significant suppression of AML cell proliferation and enhanced apoptosis. Additionally, in vivo investigations indicated that USP1 knockdown inhibited tumor growth and enhanced survival rates. The USP1 inhibitor SJB3-019A displayed similar effects on AML cells. Co-immunoprecipitation (CO-IP) coupled with mass spectrometry analysis indicated that USP1 associates with ID1, mediating its function via deubiquitination mechanisms. CUT&Tag findings additionally demonstrated that ID1 modulates target genes involved in AML. This investigation confirms that USP1 serves a critical role in facilitating the proliferation and survival of AML cells through ID1 stabilization. The findings suggest that the USP1 inhibitor SJB3-019A represents a promising new therapeutic approach for treating AML.