Multilineage mobilization of peripheral blood progenitor cells in humans following administration of PEG‐rHuMGDF
| Autor: | C. Glenn Begley, Russell L. Basser, Cindy J. O'Malley, Kerrie Clarke, Andrew P. Grigg, Michael C. Berndt, Joan O'Byrne, Rachel Mansfield, John E.J. Rasko, Sonay Hussein, William P. Sheridan, Jan Boyd |
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| Rok vydání: | 1997 |
| Předmět: |
Adult
Blood Platelets medicine.medical_specialty medicine.medical_treatment Biology Megakaryocyte Neoplasms Proto-Oncogene Proteins Internal medicine medicine Humans Cell Lineage Platelet Receptors Cytokine Progenitor cell Thrombopoietin Aged Cell Size Megakaryocytopoiesis Platelet Count Growth factor Hematology Middle Aged Hematopoietic Stem Cells Neoplasm Proteins Endocrinology medicine.anatomical_structure Bone marrow Stem cell Megakaryocytes Receptors Thrombopoietin |
| Zdroj: | British Journal of Haematology. 97:871-880 |
| ISSN: | 1365-2141 0007-1048 |
| DOI: | 10.1046/j.1365-2141.1997.1212937.x |
| Popis: | The most important physiological regulator of megakaryocytopoiesis is the ligand for the c-mpl receptor (thrombopoietin/megakaryocyte growth and development factor, MGDF). We examined the effect of pegylated-recombinant human MGDF (PEG-rHuMGDF): patients received PEG-rHuMGDF at doses of 0.03, 0.1, 0.3 or 1.0 microg/kg/d or placebo for 10d maximum in a double-blinded randomized study. There was a dose-dependent elevation in circulating platelet counts but no alteration in erythrocyte or total leucocyte counts. The number of bone marrow megakaryocytes was increased approximately 2-fold. The frequency of bone marrow progenitor cells was not altered. In contrast, both to the bone marrow results and to published pre-clinical data, there was a dose-dependent mobilization into the blood of progenitor cells of multiple cell lineages. Increased levels of Meg-CFC (maximum increase 30-fold), day 7 and day 14 GM-CFC and BFU-E were demonstrated at doses of 0.3 and 1.0 microg/kg/d PEG-rHuMGDF. At 0.1 microg/kg/d, mobilization of Meg-CFC alone occurred in two-thirds of patients. Maximum blood levels of progenitor cells occurred at day 12. Thus, administration of PEG-rHuMGDF to humans resulted in mobilization of progenitor cells of multiple lineages despite its 'lineage-specific' activity on mature cell development. |
| Databáze: | OpenAIRE |
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