Effects of interferon regulatory factor 9 on the biological phenotypes in PML-RARα-induced promyelocytic leukemia.
10.3760/cma.j.issn.0253-2727.2022.05.004
- Author:
Xue YANG
1
;
Hai Yan XING
2
;
Ke Jing TANG
2
;
Zheng TIAN
2
;
Qing RAO
2
;
Min WANG
2
;
Jian Xiang WANG
2
Author Information
1. State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Tianjin Key Laboratory of Cell Therapy for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China Yang Xue is working at the Department of Hematology, Zhongshan Hospital, Fudan University, Shanghai 200030, China.
2. State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Tianjin Key Laboratory of Cell Therapy for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
- Publication Type:Journal Article
- Keywords:
Biological function;
Interferon regulatory factor;
Leukemia, promyelocytic, acute
- MeSH:
Cell Differentiation;
Humans;
Interferon-Stimulated Gene Factor 3, gamma Subunit/metabolism*;
Leukemia, Myeloid, Acute/drug therapy*;
Leukemia, Promyelocytic, Acute/genetics*;
Oncogene Proteins, Fusion/metabolism*;
Phenotype;
Tretinoin/therapeutic use*;
U937 Cells
- From:
Chinese Journal of Hematology
2022;43(5):370-375
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the prognostic significance of interferon regulatory factor 9 (IRF9) expression and identify its role as a potential therapeutic target in acute promyelocytic leukemia (APL) . Methods: The gene expression profile and survival data applied in the bioinformatic analysis were obtained from The Cancer Genome Atlas and Beat acute myeloid leukemia (AML) cohorts. A dox-induced lentiviral system was used to induce the expression of PML-RARα (PR) in U937 cells, and the expression level of IRF9 in U937 cells treated with or without ATRA was examined. We then induced the expression of IRF9 in NB4, a promyelocytic leukemia cell line. In vitro studies focused on leukemic phenotypes triggered by IRF9 expression. Results: ①Bioinformatic analysis of the public database demonstrated the lowest expression of IRF9 in APL among all subtypes of AML, with lower expression associated with worse prognosis. ②We successfully established a PR-expression-inducible U937 cell line and found that IRF9 was downregulated by the PR fusion gene in APL, with undetectable expression in NB4 promyelocytic cells. ③An IRF9-inducible NB4 cell line was successfully established. The inducible expression of IRF9 promoted the differentiation of NB4 cells and had a synergistic effect with lower doses of ATRA. In addition, the inducible expression of IRF9 significantly reduced the colony formation capacity of NB4 cells. Conclusion: In this study, we found that the inducible expression of PR downregulates IRF9 and can be reversed by ATRA, suggesting a specific regulatory relationship between IRF9 and the PR fusion gene. The induction of IRF9 expression in NB4 cells can promote cell differentiation as well as reduce the colony forming ability of leukemia cells, implying an anti-leukemia effect for IRF9, which lays a biological foundation for IRF9 as a potential target for the treatment of APL.
