1. Department of Hematology, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, P.R. China.
2. Guizhou Province Hematopoietic Stem Cell Transplantation Center, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, P.R. China.
3. Key Laboratory of Hematological Disease Diagnostic & Treat Centre of Guizhou Province, Guiyang 550004, P.R. China.
4. School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550025, P.R. China.
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 USP1 by SJB3-019A significantly repressed cell proliferation and triggered B-ALL cell apoptosis. Finally, we found that inhibition of USP1 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.
Keywords: B-cell acute lymphoblastic leukemia, USP1, SJB3-019A, ID1, PI3K/AKT pathway, apoptosis