Effects of targeted inhibition of deubiquitinase USP7/USP47 on proliferation and apoptosis of acute myeloid leukemia cells with or without Flt3-ITD mutation
10.3760/cma.j.cn112309-20240109-00010
- VernacularTitle:靶向抑制去泛素化酶USP7/USP47对Flt3-ITD突变及非突变急性髓系白血病细胞增殖和凋亡的影响
- Author:
Qianyu ZHANG
1
;
Yu′ang GAO
;
Xin LI
;
Yongfeng SU
;
Bo CAI
;
An WANG
;
Jie ZHOU
;
Hongmei NING
Author Information
1. 安徽医科大学解放军307临床学院，安徽医科大学第五临床医学院，合肥 230032
- Keywords:
Acute myeloid leukemia (AML);
Ubiquitin-specific peptidase 7;
Flt3-ITD;
Proliferation;
AML cell line
- From:
Chinese Journal of Microbiology and Immunology
2024;44(3):217-224
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effects of ubiquitin-specific protease (USP) 7/47 inhibitor (Cat. No. 1247825-37-1) on the proliferation and apoptosis of acute myeloid leukemia (AML) cells with or without internal tandem duplications of the Flt3 gene (Flt3-ITD). Methods:ATP assay was used to detect the effects of 1247825-37-1 on the cell viability of two AML cell lines (MOLM13 and MV4-11) harboring Flt3-ITD mutation and one AML cell line (THP-1) without Flt3-ITD mutation as well as the primary Flt3-ITD-mutant and non-mutant AML cells from patient samples. Flow cytometry was used to detect the apoptosis of AML cell lines treated by different concentrations of 1247825-37-1.Results:Compared with the control group, 1247825-37-1 was able to significantly inhibit the proliferation of MOLM13, MV4-11 and THP-1 cells ( P<0.000 1). Besides, the cell viability of primary AML cells was also inhibited by 1247825-37-1, and a stronger inhibitory effect on non-mutant AML cells was observed. The USP7/USP47 inhibitor 1247825-37-1 could inhibit the proliferation of AML cells in a dose-dependent manner and a low dose (2 or 4 μmol/L) of 1247825-37-1 would be effective. Moreover, 1247825-37-1 was also able to efficiently induce the apoptosis of above AML cell lines in a dose-dependent manner. Conclusions:The USP7/USP47 inhibitor 1247825-37-1 significantly inhibits the proliferation of AML cells with or without Flt3-ITD mutation.
