Increase in peripheral blood megakaryocyte progenitors following cancer therapy with high-dose cyclophosphamide and hematopoietic growth factors
Articolo
Data di Pubblicazione:
1993
Citazione:
Increase in peripheral blood megakaryocyte progenitors following cancer therapy with high-dose cyclophosphamide and hematopoietic growth factors / S. Siena, M. Bregni, L. Bonsi, I. Sklenar, G. P. Bagnara, G. Bonadonna, A. M. Gianni. - In: EXPERIMENTAL HEMATOLOGY. - ISSN 0301-472X. - 21:12(1993 Nov), pp. 1583-90-1590.
Abstract:
Seven patients received cancer chemotherapy with high-dose cyclophosphamide (HD-CTX) associated with either recombinant human granulocyte colony-stimulating factor (rhG-CSF), rh interleukin-3 (rhIL-3), rh granulocyte-macrophage CSF (rhGM-CSF) plus rh erythropoietin (rhEpo), rhIL-3 plus rhGM-CSF, or rhIL-3 plus rhG-CSF. In the steady-state blood samples (before HD-CTX), megakaryocyte burst-forming units (BFU-Meg) and megakaryocyte colony-forming units (CFU-Meg) were virtually undetectable (< or = 1/mL BFU-Meg and CFU-Meg, range 0 to 1) by assaying unfractionated leukocytes. In contrast, in the recovery-phase blood samples (after HD-CTX), BFU-Meg and CFU-Meg increased several hundred-fold over steady-state values. This occurred regardless of the in vivo growth factors used and in parallel with increases in mixed, erythroid, and myeloid progenitors. In vitro, recovery-phase BFU-Meg and CFU-Meg responded to the novel GM-CSF/IL-3 fusion protein PIXY321 similarly as to optimal concentrations of rhIL-3 and rhGM-CSF. However, these progenitors differed from those in the steady state because BFU-Meg had faster duplication time and CFU-Meg prevailed numerically (CFU-Meg to BFU-Meg ratio 3.4 [recovery] vs. 0.52 [steady state]). Furthermore, soluble c-kit ligand/rh stem cell factor (rhSCF), in vitro in combination with rhIL-3 and rhGM-CSF or PIXY321, increased the size but not the number of colonies derived from recovery-phase BFU-Meg and CFU-Meg. These quantitative and qualitative changes occurring in circulating megakaryocyte progenitors contribute to the understanding of the rapid platelet recovery that occurs when peripheral blood hematopoietic progenitors elicited by HD-CTX and growth factor(s) are transplanted into patients treated with myeloablative chemoradiotherapy.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Proto-Oncogene Proteins c-kit; Dose-Response Relationship, Drug; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Stem Cells; Humans; Hematopoietic Cell Growth Factors; Recombinant Fusion Proteins; Stem Cell Factor; Cyclophosphamide; Antigens, CD34; Blood Cell Count; Receptor Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Granulocyte Colony-Stimulating Factor; Erythropoietin; Cells, Cultured; Interleukin-3; Antigens, CD; Adult; Receptors, Colony-Stimulating Factor; Middle Aged; Time Factors; Megakaryocytes; Cell Division
Elenco autori:
S. Siena, M. Bregni, L. Bonsi, I. Sklenar, G. P. Bagnara, G. Bonadonna, A. M. Gianni
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