Detection and quantification of functionally defined hematopoietic progenitor cells and tissue specific mRNA within the peripheral blood of myeloma patients after administration of granulocyte colony-stimulating factor and erythropoietin |
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Authors: | Grassinger Jochen Mueller Gunnar Hart Christina Nilsson Susie K Haylock David N Andreesen Reinhard Hennemann Burkhard |
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Affiliation: | Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany;;Australian Stem Cell Centre, Clayton, Vic., Australia |
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Abstract: | Objective: Hematopoietic progenitor cells (HPC) as well as tissue committed stem cells expressing mRNA specific to various somatic tissues are thought to be part of the CD34+ bone marrow compartment. In this study, we explore and quantify their mobilization in patients with multiple myeloma undergoing chemotherapy upon administration of granulocyte colony-stimulating factor (G-CSF) plus/minus erythropoietin (EPO). Patients and methods: HPC were quantified by flow cytometry and functional assays within the blood of healthy donors and myeloma patients before and after chemotherapy followed by G-CSF or G-CSF + EPO given subcutaneously. The mRNA expression was studied by quantitative polymerase chain reaction (PCR). Cytokines and peripheral blood protease levels were measured by an enzyme-linked immunosorbent assay. Results: EPO did not significantly alter the number of HPC mobilized by G-CSF alone, and mRNA specific for liver, brain, muscle and kidney was detected in both treatment groups. Quantitative PCR analysis revealed a 2.7-fold increased expression of glial fibrillary acidic protein after G-CSF + EPO administration compared to G-CSF alone ( P = 0.003). The concentration of G-CSF rose from 62 ± 22 pg/mL and 48 ± 10 pg/mL to 28 ± 9 ng/mL and 85 ± 10 ng/mL after 10 d of treatment with G-CSF and G-CSF + EPO, respectively. The concentration of neutrophil elastase (NE) rose only in the G-CSF group by a factor 1.5. Conclusion: The alteration of G-CSF and NE levels as well as the expression of tissue committed RNA after the administration of EPO in addition to G-CSF indicate that different growth factors mobilize different stem cells that might potentially be used for the support of tissue repair in future treatment protocols. |
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Keywords: | hematopoietic stem cells mobilization granulocyte colony-stimulating factor erythropoietin |
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