title: 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.
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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Grassinger
authors.forename: Gunnar
authors.initials: G
authors.lastname: Mueller
authors.forename: Christina
authors.initials: C
authors.lastname: Hart
authors.forename: Susie K
authors.initials: SK
authors.lastname: Nilsson
authors.forename: David N
authors.initials: DN
authors.lastname: Haylock
authors.forename: Reinhard
authors.initials: R
authors.lastname: Andreesen
authors.forename: Burkhard
authors.initials: B
authors.lastname: Hennemann
mesh_terms: D018952:Antigens, CD34; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001773:Blood Cells; D016022:Case-Control Studies; D002452:Cell Count; D016207:Cytokines / Q000097:blood; D004921:Erythropoietin / Q000008:administration & dosage* / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D019272:Leukocyte Elastase / Q000097:blood; D009101:Multiple Myeloma / Q000628:therapy*; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis* / Q000187:drug effects
chemical_list: D018952:Antigens, CD34; D016207:Cytokines; D012333:RNA, Messenger; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D019272:Leukocyte Elastase