Delineation of cell cycle state and correlation to adhesion molecule expression of human CD34+ cells from steady-state bone marrow and peripheral blood mobilized following G-CSF-supported chemotherapy
Treatment with a combination of chemotherapy and G-CSF leads to the release of hematopoietic stem cells from the bone marrow (BM) to the peripheral blood (PB), where they can be harvested for transplantation. Premobilization BM CD34+ cells were reported to proliferate actively, while virtually none...
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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
01 July 1998
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| In: |
Stem cells
Year: 1998, Volume: 16, Issue: 4, Pages: 271-279 |
| ISSN: | 1549-4918 |
| DOI: | 10.1002/stem.160271 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1002/stem.160271
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| Author Notes: | Stefan Fruehauf, Marlon R. Veldwijk, Alwin Krämer, Rainer Haas, W. Jens Zeller |
MARC
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| 520 | |a Treatment with a combination of chemotherapy and G-CSF leads to the release of hematopoietic stem cells from the bone marrow (BM) to the peripheral blood (PB), where they can be harvested for transplantation. Premobilization BM CD34+ cells were reported to proliferate actively, while virtually none of the mobilized PB CD34+ cells were in the S/G2M phase. We were interested in elucidating the cell cycle state further and in investigating the role of adhesion molecule expression on marrow-adherent and circulating CD34+ cells during different phases of the cell cycle. Consecutive premobilization BM and leukapheresis product (LP) samples were obtained from 14 patients following G-CSF-supported chemotherapy. Steady-state BM and LP CD34+ selected cells were triple-stained for CD34, for DNA using the intercalating dye 7-aminoactinomycin D, and for Ki-67, cyclins, or adhesion antigens. Ki-67 is expressed in all phases of the cell cycle except G0 and was found in 69.14% ± 3.46% (mean ± standard error [SE]) of BM CD34+ cells and 62.78% ± 3.37% of LP CD34+ cells, while in BM significantly more CD34+/Ki-67+ cells were in the S/G2M phase of the cell cycle than in LP (8.6% ± 0.9% versus 1.8% ± 0.3%, respectively, p = 0.0001). Therefore, most circulating mobilized CD34+ cells are in the G1 phase, similar to their steady-state BM counterparts. Cyclin A became detectable in the 2n DNA peak. As expected, a higher proportion of CD34+/cyclin A+/S/G2M cells was found in BM than in LP (p < 0.05). Antigen density of the cyclins D3 and D2 tended to be higher on LP than on BM CD34+ cells, while D1 was found at low levels in similar density. The adhesion antigens CD18, CD49b, CD49d, CD49e, CD58, and CD62L were expressed in a significantly higher proportion of S/G2M-phase than in G0/G1-phase CD34+ cells. The strongest association to the proliferative status was observed for CD49d, which was coexpressed by 85.9% ± 2.6% (BM) or 90.8% ± 2.5% (LP) of CD34+/S/G2M cells, whereas a distinct CD34+/CD49d−/S/G2M population could not be detected. The average coexpression of the other antigens was 57% (CD49e, CD18) or lower. Our results demonstrate that the majority of PB CD34+ cells mobilized following G-CSF-supported chemotherapy and steady-state BM CD34+ cells are in the late G1 phase of the cell cycle and show a correlation between the expression of adhesion receptors and cell cycle status of CD34+ cells in both BM and LP. | ||
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