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.
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.
Grassinger
Jochen
J
Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany.
Mueller
Gunnar
G
Hart
Christina
C
Nilsson
Susie K
SK
Haylock
David N
DN
Andreesen
Reinhard
R
Hennemann
Burkhard
B
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
D018952:Antigens, CD34; D016207:Cytokines; D012333:RNA, Messenger; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D019272:Leukocyte Elastase