NPM1-Mutated Patient-Derived AML Cells Are More Vulnerable to Rac1 Inhibition.

ABSTRACT: The prognosis of acute myeloid leukemia (AML) is poor, especially for the elderly population. Targeted therapy with small molecules may be a potential strategy to overcome chemoresistance and improve survival in AML. We investigated the inhibition of the signaling molecule ras-related C3 botulinum toxin substrate 1 (Rac1) in leukemia cells derived from 79 consecutive AML patients, using five Rac1 inhibitors: ZINC69391, ITX3, EHOP-016, 1A-116, and NSC23766. In vitro cell proliferation and apoptosis assays and the assessment of cytokine profiles in culture media were conducted. All five inhibitors had an antiproliferative effect; IC₅₀ ranged from 3-24 µM. They induced significant apoptosis and necrosis compared to the untreated controls (p < 0.0001) at concentrations aro

SUBMITTER: Hemsing AL 

PROVIDER: S-EPMC9405324 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature