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[Role of Ca 2+-NFAT Signaling Pathway in Ph + ALL Drug-resistance Mediated by Bone Marrow Stromal Cells]

[Role of Ca 2+-NFAT Signaling Pathway in Ph + ALL Drug-resistance Mediated by Bone Marrow Stromal Cells]

Huan-Xin Zhang, Ya-Hui Han, Ting-Ting Qiu, Yao Yao, Sheng-Yun Zhu, Ming-Shan Niu, Ling-Yu Zeng, Zhen-Yu Li, Zhi-Ling Yan, Kai-Lin Xu

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2019 Jun;27(3):717-722.

PMID: 31204921

Abstract:

Objective:
To explore the role of Ca2+-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 Ca2+ 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 Ca2+ 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 Ca2+-NFAT signaling pathway, reduce the protective effect of OP9 on Sup-B15 cells.Conclution:The Ca2+-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 Ca2+-NFAT signaling pathway.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP121714225-A	FLUO 3/AM - CAS 121714-22-5		121714-22-5	Price

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