Expression of adhesion molecules on CD34(+) cells in peripheral blood of non-hodgkin's lymphoma patients mobilized with different growth factors.
Adhesion molecules on CD34(+) cells were implicated in the process of peripheral blood stem cell (PBSC) mobilization and homing. We studied the mobilization of CD34(+)Thy1(+) cells, CD34(+) very late-acting antigen (VLA)4(+) cells, and CD34(+)L-selectin(+) cells in non-Hodgkin's lymphoma patients mobilized with cyclophosphamide plus G-CSF, GM-CSF, or GM-CSF followed by G-CSF. The mean percentage of CD34(+) cells in the bone marrow (BM) expressing Thy1 was 23.6% +/- 11% and 17.8% +/- 8% in the PB before mobilization, and was markedly decreased to 4.5% +/- 3.3% in the apheresis collections. Similarly, the mean percentage of CD34(+) cells expressing L-selectin was 35.8% +/- 4.3% in the BM, 21.6% +/- 4.1% in the PB before mobilization and was markedly decreased to 9.1% +/- 2.5% in the apheresis collections. Patients in the three arms of the study had a similar pattern of CD34(+)Thy1(+) and CD34(+)L-selectin(+) cell mobilization. Also, a similar pattern of coexpression of CD34(+)Thy1(+) and CD34(+)L-selectin(+) cells was observed when the patients were regrouped as "good mobilizers" (> or =2 x 10(6) CD34(+)CD45(dim) cells/kg, in four collections) and "poor mobilizers" (<0.4 x 10(6) CD34(+)CD45(dim) cells/kg, in two collections). The mean percentage of CD34(+) cells expressing VLA-4 in the BM and PB was relatively high (73.4% +/- 12% and 65.4% +/- 6.6%, respectively) and dropped considerably in the PBSC collections to 43.5% +/- 7.1% with a similar pattern observed for patients in arms A, B, and C. However, when the patients were regrouped as "good mobilizers" and "poor mobilizers," a higher percentage of CD34(+) cells expressing VLA-4 was observed in the PBSC of the pooled "good mobilizers" (50.5% +/- 9% versus 36.3% +/- 6.4%; p = 0.01). We conclude that release of CD34(+) cells to the PB involves a general downregulation of Thy1, L-selectin and VLA-4 on CD34(+) cells, irrespective of the growth factor used for mobilization. However, good mobilizers had a relatively higher percentage of CD34(+) cells expressing the VLA-4 antigen.
Gazitt
Y
Y
University of Texas Health Science Center and Wilford Hall Medical Center, San Antonio, Texas 78284, USA.
Shaughnessy
P
P
Liu
Q
Q
D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000096:biosynthesis*; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000096:biosynthesis*; D019041:L-Selectin / Q000096:biosynthesis*; D008228:Lymphoma, Non-Hodgkin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis*
D018952:Antigens, CD34; D018906:Antineoplastic Agents, Alkylating; D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D019041:L-Selectin; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide