AMD3100, a competitive antagonist of CXCR-4, disrupts the binding of its ligand, stromal cell-derived factor-1 (SDF-1), and facilitates stem cell mobilisation in patients with haematological malignancies. This study investigated the differential kinetics of CXCR-4 and adhesion molecule expression and their impact on stem cell yield during mobilisation with granulocyte-colony stimulating factor (G-CSF) (days 1-4) followed by AMD3100 in 10 patients with multiple myeloma. A four-colour flow cytometry-based determination of CXCR-4, VLA-4, L-selectin, PECAM, LFA-1 and CD44 expression on CD34+ cells and measurement of SDF-1 concentration were performed at different time points. After G-CSF alone, CXCR-4 expression on patients' blood and marrow CD34+ cells was significantly lower than in the healthy controls (p < 0.001), but allowed no prediction of stem cell yield. Except in the single poorly mobilising patient, AMD3100 led to a further significant decrease of CXCR4 (p = 0.001), which inversely correlated with the CD34+ counts in the blood (p = 0.005). SDF-1 level in patients' marrow was positively correlated with CXCR-4 expression on CD34+ cells (p = 0.011). It is interesting to note that the expression of adhesion molecules remained unaffected by AMD3100 administration. Further studies will define the possible prognostic role of AMD3100 mediated changes in CXCR-4 expression for the prediction of stem cell yield attainable with this new mobilisation regimen.

译文

AMD3100,CXCR-4的竞争性拮抗剂,破坏其配体基质细胞衍生因子1 (SDF-1) 的结合,并促进血液系统恶性肿瘤患者的干细胞动员。这项研究调查了10例多发性骨髓瘤患者在使用粒细胞集落刺激因子 (g-csf) 动员 (第1-4天) 和AMD3100动员期间CXCR-4和粘附分子表达的差异动力学及其对干细胞产量的影响。在不同时间点进行基于四色流式细胞仪的CD34细胞上CXCR-4,VLA-4,L-选择素,PECAM,LFA-1和CD44表达的测定以及SDF-1浓度的测量。单独使用g-csf后,患者血液和骨髓CD34细胞上的CXCR-4表达显着低于健康对照组 (p <0.001),但无法预测干细胞产量。除了单个动员不良的患者外,AMD3100导致CXCR4进一步显着降低 (p = 0.001),这与血液中的CD34计数成反比 (p = 0.005)。患者骨髓SDF-1水平与CD34 + 细胞CXCR-4表达呈正相关 (p = 0.011)。有趣的是,粘附分子的表达不受AMD3100给药的影响。进一步的研究将确定AMD3100介导的CXCR-4表达变化对于预测这种新的动员方案可获得的干细胞产量的可能的预后作用。

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