Plasma levels of SDF-1 and expression of SDF-1 receptor on CD34+ cells in mobilized peripheral blood of non-Hodgkin's lymphoma patients.
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.
Gazitt
Y
Y
Department of Medicine/Hematology, University of Texas Health Science Center, San Antonio, Texas 78284, USA. gazitt@uth-scsa.edu
Liu
Q
Q
D018952:Antigens, CD34 / Q000032:analysis*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D001781:Blood Component Removal; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000097:blood*; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage; D006412:Hematopoietic Stem Cells / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D019718:Receptors, CXCR4 / Q000032:analysis / Q000096:biosynthesis*
D018952:Antigens, CD34; D018906:Antineoplastic Agents, Alkylating; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D008565:Membrane Proteins; D019718:Receptors, CXCR4; C084881:flt3 ligand protein; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide