Peking University Institute of Hematology, Peking University People's Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People's Republic of China.
Int J Hematol. 2011 Jun;93(6):750-759. doi: 10.1007/s12185-011-0869-9. Epub 2011 May 24.
Chemokine stromal-derived factor-1 (SDF-1) and its receptor CXCR4 have been shown to play an important role in the migration and homing of the transplanted hematopoietic stem cells (HSCs). Mesenchymal stem cells (MSCs) express these molecules. This study is to test the hypothesis that acute myeloid leukemia (AML) alters the expression of SDF-1/CXCR4 in human bone marrow MSCs. Expression of both CXCR4 and SDF-1 was found to be increased, but excessively retained, in the MSCs in AML. In contrast, the SDF-1 level in bone marrow plasma and supernatant of cultured MSCs from AML patients were reduced, while the SDF-1 was able to efficiently induce a dose-dependent migration of MSCs in vitro. Our results demonstrate that altered expression and distribution of SDF-1/CXCR4 in MSCs may contribute to SDF-1 deficiency in the plasma of AML patients. The migration of MSCs may be negatively affected by the SDF-1 deficiency.
趋化因子基质衍生因子-1(SDF-1)及其受体 CXCR4 已被证明在移植的造血干细胞(HSCs)的迁移和归巢中发挥重要作用。间充质干细胞(MSCs)表达这些分子。本研究旨在检验急性髓系白血病(AML)改变人骨髓间充质干细胞中 SDF-1/CXCR4 表达的假说。结果发现,AML 中的 MSC 中 CXCR4 和 SDF-1 的表达均增加,但过度保留。相比之下,AML 患者骨髓血浆和培养的 MSC 上清液中的 SDF-1 水平降低,而 SDF-1 能够有效地诱导 MSC 在体外的剂量依赖性迁移。我们的结果表明,MSC 中 SDF-1/CXCR4 的表达和分布改变可能导致 AML 患者血浆中 SDF-1 缺乏。MSC 的迁移可能会受到 SDF-1 缺乏的负面影响。