Gazitt Y, Liu Q
Department of Medicine/Hematology, University of Texas Health Science Center, San Antonio, Texas 78284, USA.
Stem Cells. 2001;19(1):37-45. doi: 10.1634/stemcells.19-1-37.
CXCR4 is the receptor for the chemokine stromal derived factor-1 (SDF-1), is expressed on CD34+ cells, and has been implicated in the process of CD34+ cell migration and homing. We studied the mobilization of CD34/CXCR4 cells and the plasma levels of SDF-1 and flt3-ligand (flt3-L) in 36 non-Hodgkin's lymphoma patients receiving cyclophosphamide (Cy) plus G-CSF (arm A), Cy plus GM-CSF (arm B), or Cy plus GM-CSF followed by G-CSF (arm C) for peripheral blood stem cell (PBSC) mobilization and autotransplantation. We observed lower plasma levels of SDF-1 in PBSCs compared to premobilization bone marrow samples. The mean plasma SDF-1 levels were similar in PBSC collections in the three arms of the study. In contrast, SDF-1 levels in the apheresis collections of the "good mobilizers" (patients who collected a minimum of 2 x 10(6) CD34+ cells/kg in one to four PBSC collections) were significantly lower than the apheresis collections of the "poor mobilizers" (> or = 0.4 x 10(6) CD34+ cells/kg in the first two PBSC collections; 288 +/- 82 pg/ml versus 583 +/- 217 pg/ml; p = 0.0009). The mean percentage of CD34+ cells expressing CXCR4 in the apheresis collections was decreased in the PBSC collections compared with premobilization values from 28% to 19.4%. Furthermore, the percentage of CD34+ cells expressing CXCR4 in the good mobilizers was significantly lower compared with the poor mobilizers (14.7 +/- 2.1% versus 33.6 +/- 2.1%; p = 0.002). The good mobilizers had also significantly lower levels of flt3-L compared with the poor mobilizers (34 +/- 4 pg/ml versus 106 +/- 11 pg/ml; p = 0.006), Finally, the levels of flt3-L strongly correlated with SDF-1 levels (r = 0.8; p < 0.0001). We conclude: A) low plasma levels of SDF-1 and low expression of CXCR4 characterize patients with good mobilization outcome, and B) the levels of SDF-1 correlate with flt3-L, suggesting an association of these cytokines in mobilization of CD34+ cells.
CXCR4是趋化因子基质衍生因子-1（SDF-1）的受体，在CD34+细胞上表达，并参与CD34+细胞迁移和归巢过程。我们研究了36例接受环磷酰胺（Cy）加粒细胞集落刺激因子（G-CSF）（A组）、Cy加粒细胞-巨噬细胞集落刺激因子（GM-CSF）（B组）或Cy加GM-CSF后加G-CSF（C组）进行外周血干细胞（PBSC）动员和自体移植的非霍奇金淋巴瘤患者中CD34/CXCR4细胞的动员情况以及SDF-1和fms样酪氨酸激酶3配体（flt3-L）的血浆水平。我们观察到与动员前骨髓样本相比，PBSC中SDF-1的血浆水平较低。研究的三个组中PBSC采集时的平均血浆SDF-1水平相似。相比之下，“良好动员者”（在一至四次PBSC采集中至少采集2×10⁶个CD34+细胞/kg的患者）的单采血浆中SDF-1水平显著低于“不良动员者”（在前两次PBSC采集中≥0.4×10⁶个CD34+细胞/kg；288±82 pg/ml对583±217 pg/ml；p = 0.0009）。与动员前相比，PBSC采集中单采血浆中表达CXCR4的CD34+细胞的平均百分比从28%降至19.4%。此外，良好动员者中表达CXCR4的CD34+细胞百分比显著低于不良动员者（14.7±2.1%对33.6±2.1%；p = 0.002）。良好动员者的flt3-L水平也显著低于不良动员者（34±4 pg/ml对106±11 pg/ml；p = 0.006）。最后，flt3-L水平与SDF-1水平密切相关（r = 0.8；p < 0.0001）。我们得出结论：A）血浆SDF-1水平低和CXCR4表达低是动员效果良好患者的特征，B）SDF-1水平与flt3-L相关，提示这些细胞因子在CD34+细胞动员中存在关联。
