Biological behavior of SDF-1/CXCR4 in patients with myelodysplastic syndrome.
- Author:
Rui YANG
1
;
Jie PU
;
Juan GUO
;
Feng XU
;
Zheng ZHANG
;
You-Shan ZHAO
;
Xi ZHANG
;
Shu-Cheng GU
;
Chun-Kang CHANG
;
Xiao LI
Author Information
1. Department of Hematology, Shanghai Jiaotong University, Shanghai, China.
- Publication Type:Journal Article
- MeSH:
Apoptosis;
Bone Marrow Cells;
metabolism;
Cell Adhesion;
Cell Line;
Chemokine CXCL12;
metabolism;
Humans;
Myelodysplastic Syndromes;
metabolism;
Receptors, CXCR4;
metabolism;
Signal Transduction
- From:
Journal of Experimental Hematology
2011;19(6):1432-1437
- CountryChina
- Language:Chinese
-
Abstract:
The purpose of this study was to evaluate the biological behavior of stromal cell-derived factor-1 (SDF-1) in migration, adhesion and apoptosis as well as the related signaling transduction pathways in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). 37 patients with MDS, 10 patients with de novo AML and 14 patients with non-clonal cytopenia diseases were chosen for this study. The expression level of CXCR4 on CD34(+) cells and apoptosis of CD34(+) cells in bone marrow were detected by flow cytometry; the chemotaxis of SDF-1 on bone marrow mononuclear cells in 4 patients with low risk MDS (IPSS score ≤ 1.0) and 5 patients with high risk MDS (IPSS score ≥ 1.5) was assayed by transwell migration test of cells. The effect of SDF-1 on cell adhesion capability was measured by using CCK-8 method. The results indicated that the apoptosis rate of CD34(+) cells was significantly higher in MDS patients with low risk (IPPS score < 1.0) than that in MDS patients with high risk (IPSS score ≥ 1.5) (21.55% vs 7.52%, p < 0.001); as well, the apoptosis rate of CD34(+) cells was significantly higher in MDS patients with low risk than that in de novo AML patients (21.55% vs 7.33%, p < 0.001), no relation of CD34(+) cell apoptosis with age and sex of patients was found. SDF-1 could promote the cells of patients with CXCR4 high expression to adhere to the stroma cells, and induce migration of these cells, as well as, SDF-1 could trigger the polarization of the cells which highly expressed CXCR4. After addition of pertussis toxin, wortmannin and AMD3100, the ability of adhersion and migration of the cells with highly expressed CXCR4 decreased, but there was no above-mentioned phenomenon in patients who lowly expressed CXCR4. It is concluded that the SDF-1/CXCR4 axis enhances the ability of cell adhesion and migration through PI3K signaling pathway, thereby plays antiapoptosis role, moreover the above-mentioned effects can be blocked by PI3K pathway inhibitor and G protein inhibitor.
