Role of Ca-NFAT Signaling Pathway in Ph ALL Drug-resistance Mediated by Bone Marrow Stromal Cells.
10.19746/j.cnki.issn.1009-2137.2019.03.012
- Author:
Huan-Xin ZHANG
1
,
2
;
Ya-Hui HAN
2
,
3
;
Ting-Ting QIU
2
,
3
;
Yao YAO
2
,
3
;
Sheng-Yun ZHU
2
,
3
;
Ming-Shan NIU
2
,
3
;
Ling-Yu ZENG
2
,
3
;
Zhen-Yu LI
2
,
3
;
Zhi-Ling YAN
3
,
4
;
Kai-Lin XU
1
,
5
Author Information
1. The First Clinical Medical College, Nanjing Medical University，Nanjing 210029, Jiangsu Province, China,Department of Hematology
2. The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China.
3. Department of Hematology
4. The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China,E-mail: hematology_md@126.com.
5. The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China,E-mail:lihmd@163.com.
- Publication Type:Journal Article
- MeSH:
Bone Marrow Cells;
Cell Line, Tumor;
Humans;
Imatinib Mesylate;
Mesenchymal Stem Cells;
NFATC Transcription Factors;
Precursor Cell Lymphoblastic Leukemia-Lymphoma;
Signal Transduction
- From:
Journal of Experimental Hematology
2019;27(3):717-722
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the role of Ca-NFAT signaling pathway in Ph-ALL drug resistance mediated by bone marrow stromal cells.
METHODS:The transcription level of NFAT mRNA in Sup-B15 cells and Ph ALL primary cells was detected by polymerase chain reaction. The expression of P-glycoprotein in Sup-B15 cells was detected by flow cytometry. The change of NFAT protein in Sup-B15 cells was detected by Western blot. AnnexinV/7-AAD was used to label cells. Flow cytometry was used to detect cell apoptosis; Fluo 3-AM dye was used to label cells, and flow cytometry used to detect changes of Ca concentration in leukemia cells.
RESULTS:NFAT expression could be detected in both Sup-B15 and Ph ALL primary cells; P-glycoprotein could not be detected by flow cytometry; CAS could significantly inhibit NFAT protein expression in clinically applied drug concentrations (2.5, 5 μmol/L); Clinically applied concentration of CAS (2.5, 5 μmol / L) has no significant effect on the apoptosis of Sup-B15 cells, while higher concentration of CAS (10 μmol / L) could induce apoptosis of Sup-B15 cells. Bone marrow stromal cells OP9 could, decrease the sensitivity of Sup-B15 cells and Ph ALL primary cells to imatinib (IM); After co-culture with bone were marrow stromal cells, the Ca concentration in Sup-B15 cells was enhanced, the levels of NFAT protein and nullear protein in sup-B15 cells also were enhanced. The addition of CAS in co-culture system could inlibit the Ca-NFAT signaling pathway, reduce the protective effect of OP9 on Sup-B15 cells.Conclution:The Ca-NFAT sigualing pathway, contributes to the survival of Ph ALL cells. Bone marrow stromal cells can mediate the resistance of Ph ALL cells to IM by activating Ca-NFAT signaling pathway.
