title: Cell cycle modulation by hematopoietic growth factors in myelodysplastic syndromes: analysis by three-color flow cytometry.
abstract: Investigations of the effects of hematopoietic growth factors (HGFs) on the cell cycle of cells from myelodysplastic syndrome (MDS) have been hampered by technical difficulties. In this study, using a recently established flow cytometric method that enables detailed analysis of the cell cycle (Gzero-, G1-, S-, and G2/M-phases) of target cells in a heterogeneous cell population, we examined the effects of granulocyte colony-stimulating factor (G-CSF) and other HGFs on the cell cycle of CD13-positive cells (blasts and other malignant myelocytic and monocytic cells) in MDS. The cell cycle response to G-CSF (decrease in Gzero-phase cells and increase in S-phase cells) was heterogeneous among MDS cases. When the data for 13 MDS cases and 15 de novo AML cases were compared statistically, the magnitude of cell cycle activation by G-CSF was weaker for the cells from the MDS cases. Stem cell factor, interleukin-3, or a combination of these HGFs with G-CSF reduced the Gzero-phase cell percentage in all examined MDS cases whose cell cycle was unresponsive to G-CSF alone. When cytosine arabinoside was added to cells with or without stimulation by HGFs, the viable G0-phase cell count was reduced in HGF-stimulated cells compared with unstimulated cells in seven of eight cases. The present results suggest that G-CSF-induced cell cycle stimulation of malignant cells can be expected in a fraction of MDS patients and that even in MDS patients whose cells do not respond to G-CSF, employment of other HGFs and their combination with G-CSF is worth consideration. The results also suggest that a well-designed therapy using HGFs and chemotherapeutic drugs may reduce the quiescent (Gzero) cell count in MDS, which is assumed to be responsible for drug resistance derived from cell kinetics.
authors.affiliation: Third Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ogata
authors.forename: E
authors.initials: E
authors.lastname: An
authors.forename: K
authors.initials: K
authors.lastname: Kamikubo
authors.forename: H
authors.initials: H
authors.lastname: Tamura
authors.forename: N
authors.initials: N
authors.lastname: Yokose
authors.forename: K
authors.initials: K
authors.lastname: Dan
authors.forename: T
authors.initials: T
authors.lastname: Nomura
mesh_terms: D002453:Cell Cycle / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry / Q000379:methods*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000473:pathology*
chemical_list: D016179:Granulocyte Colony-Stimulating Factor