Inhibition of USP1 induces apoptosis via ID1/AKT pathway in B-cell acute lymphoblastic leukemia cells

Deubiquitylating enzyme ubiquitin-specific protease 1 (USP1) has been reported to be aberrantly overexpressed in cancers, and it plays a critical role in regulating various cellular processes, such as cell proliferation, apoptosis, and cell differentiation. However, the role of USP1 in B-cell acute lymphoblastic leukemia (B-ALL) remains largely undefined. USP1 expression in 30 newly diagnosed B-ALL patients was detected by real-time PCR and western blot. We found that USP1 was generally upregulated in the bone marrow cells derived from B-ALL patients. Knockdown of USP1 by siRNA decreased B-ALL cell growth and induced apoptosis. Similarly, pharmacological inhibition of USPI by SJB3-019A significantly repressed cell proliferation and triggered B-ALL cell apoptosis. Finally, we found that inhibition of USPI downregulated the expression of ID1 and p-AKT, and upregulated ID1 expression could reverse the suppressive effects of USP1 inhibitor in B-ALL cells. Taken together, these results demonstrate that USP1 promote B-ALL progression at least partially via the ID1/AKT signaling pathway, and USP1 inhibitors might be promising therapeutic application for B-ALL.

Automated summary

Deubiquitylating enzyme USP1 is overexpressed in B-ALL patients, promoting disease progression through the ID1/AKT signaling pathway. Inhibiting USP1 suppresses cell proliferation and induces apoptosis, suggesting promising therapeutic potential.