Inhibition of ubiquitin-specific protease 7 sensitizes acute myeloid leukemia to chemotherapy.

ABSTRACT: Resistance of acute myeloid leukemia (AML) to therapeutic agents is frequent. Consequently, the mechanisms leading to this resistance must be understood and addressed. In this paper, we demonstrate that inhibition of deubiquitinylase USP7 significantly reduces cell proliferation in vitro and in vivo, blocks DNA replication progression and increases cell death in AML. Transcriptomic dataset analyses reveal that a USP7 gene signature is highly enriched in cells from AML patients at relapse, as well as in residual blasts from patient-derived xenograft (PDX) models treated with clinically relevant doses of cytarabine, which indicates a relationship between USP7 expression and resistance to therapy. Accordingly, single-cell analysis of AML patient samples at relapse versus at diagnosis showed t

SUBMITTER: Cartel M 

PROVIDER: S-EPMC7245510 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature