Effect of Dimethyl Fumarate (DMF) on T-cell Acute Lymphoblastic Leukemia.
10.19746/j.cnki.issn.1009-2137.2022.01.01
- Author:
Jin-Ge XU
1
;
Qiao CHENG
2
;
Gui-Hua ZHANG
3
;
Li-Ping KONG
3
;
Li LI
3
;
Kai-Ge LIU
3
;
Jin-Yan WU
3
;
Qiu-Rong ZHANG
3
Author Information
1. Department of Hematology, The Second Affiliated Hospital of Xuzhou Medical University, General Hospital of Xuzhou Coal Mining Group, Xuzhou 221006, Jiangsu Province, China,E-mail: xjg53@qq.com.
2. Department of Hematology, The First Affiliated Hospital of Soochow University, Suzhou 215000, Jiangsu Province, China.
3. Department of Hematology, The Second Affiliated Hospital of Xuzhou Medical University, General Hospital of Xuzhou Coal Mining Group, Xuzhou 221006, Jiangsu Province, China.
- Publication Type:Journal Article
- Keywords:
HACE1;
T-cell acute lymphoblastic leukemia;
dimethyl fumarate;
nuclear factor-erythroid 2-related factor 2
- MeSH:
Dimethyl Fumarate/pharmacology*;
HEK293 Cells;
Humans;
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma;
T-Lymphocytes;
Ubiquitin-Protein Ligases
- From:
Journal of Experimental Hematology
2022;30(1):1-5
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the effect and possible mechanism of dimethyl fumarate (DMF) on T-cell acute lymphoblastic leukemia (T-ALL), and provide experimental and theoretical basis for the clinical treatment of T-ALL.
METHODS:Jurkat cells were treated with different concentrations of DMF for 24 hours, and then the proportion and absolute count of Ki67-positive Jurkat cells were analyzed by flow cytometry. Meanwhile, the protein levels of nuclear factor-erythroid 2-related factor 2 (Nrf2) and E3 ubiquitin ligase HACE1 in Jurkat cells treated with DMF for 24 hours were evaluated by Western blot. Nrf2 proteins were co-immunoprecipitated in Jurkat cells, and then HACE1 protein was assessed by Western blot. Plasmids of Flag-Nrf2 and different gradients of Flag-HACE1 were transfected into HEK293T cells, and the levels of Flag-Nrf2 were detected by Western blot after 48 hours.
RESULTS:DMF could significantly inhibit the proportion and absolute count of Ki67-positive Jurkat cells, and DMF inhibited the proliferation of Jurkat cells in a dose-dependent manner (r=0.9595, r=0.9054). DMF could significantly up-regulate the protein levels of Nrf2 and E3 ubiquitin ligase HACE1 in Jurkat cells (P<0.01, P<0.01). HACE1 physically interacted with Nrf2 in Jurkat cells. Overexpression of Flag-HACE1 significantly increased the protein level of Flag-Nrf2 in a dose-dependent manner (r=0.9771).
CONCLUSION:DMF inhibits the proliferation of T-cell acute lymphoblastic leukemia cell. The mechanism may be that, DMF significantly up-regulates the protein levels of Nrf2 and E3 ubiquitin ligase HACE1, and HACE1 interacts with Nrf2 and positively regulates Nrf2 protein level.
