Department of Hematology, Shanghai Sixth People's Hospital Affiliated of Shanghai Jiaotong University, 200233 Shanghai, China.
Med Oncol. 2012 Jun;29(2):1202-8. doi: 10.1007/s12032-011-9943-7. Epub 2011 May 10.
The purpose of this investigation is to evaluate the biological behavior of stromal cell-derived factor-l (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). We chose 22 patients with MDS, 7 patients with de novo AML, and 8 patients with non-clonal cytopenia diseases. We performed flow cytometric analysis of CD34(+) cells apoptosis using annexinV-FITC, which binds to exposed phosphatidylserine on apoptotic cells. The cell adhesion capability was detected by CCK-8 assay. The migration ability of the cell was checked by transwell assay. Furthermore, we measured SDF-1 levels in BM plasma from patients by enzyme-linked immunosorbent assay (ELISA). Our results indicated that the apoptosis of CD34(+) cell was significantly increased in the Low-grade MDS (IPSS score ≤ 1.0) patients compared with the high-grade MDS (IPSS score ≥ 1.5) (21.33% vs. 7.27%, P < 0.001) and patients with de novo AML (21.33% vs. 7.53%, P < 0.001). SDF-1 promoted CXCR4 high expression cells adhesion to the stroma cells (MSC) and induced these cells migration. SDF-1 could trigger the occurrence of polarized morphology of the cells that expressed CXCR4 high. After addition of wortmannin or PTX, the ability of adhesion and migration of the cells that expressed CXCR4 high decreased. But in the patient's cells that expressed CXCR4 low, there was no above-mentioned phenomenon. So we can suppose that the signaling pathway of SDF-1/CXCR4 axis is PI3K pathway, and we should do more things about this pathway and may find out the target treatment of MDS.
本研究旨在评估骨髓增生异常综合征（MDS）和急性髓系白血病（AML）患者基质细胞衍生因子-1（SDF-1）在迁移、黏附和凋亡中的生物学行为，以及相关的信号转导通路。我们选择了 22 例 MDS 患者、7 例初发 AML 患者和 8 例非克隆性细胞减少症患者。采用流式细胞术检测 AnnexinV-FITC 标记的 CD34+细胞凋亡，该方法可以与凋亡细胞暴露的磷脂酰丝氨酸结合。通过 CCK-8 检测细胞黏附能力，Transwell 检测细胞迁移能力。此外，通过酶联免疫吸附试验（ELISA）检测患者骨髓血浆中的 SDF-1 水平。我们的结果表明，低危 MDS（IPSS 评分≤1.0）患者的 CD34+细胞凋亡明显高于高危 MDS（IPSS 评分≥1.5）患者（21.33% vs. 7.27%，P<0.001）和初发 AML 患者（21.33% vs. 7.53%，P<0.001）。SDF-1 促进 CXCR4 高表达细胞与基质细胞（MSC）黏附，并诱导这些细胞迁移。SDF-1 可引发表达 CXCR4 高的细胞发生极化形态。加入wortmannin 或 PTX 后，表达 CXCR4 高的细胞黏附和迁移能力下降。但在表达 CXCR4 低的患者细胞中，没有上述现象。因此，我们可以假设 SDF-1/CXCR4 轴的信号通路是 PI3K 通路，我们应该对该通路进行更多的研究，可能会发现 MDS 的靶向治疗方法。
