The effects of interleukin-3, GM-CSF, and G-CSF on the growth kinetics of colony-forming cells in myelodysplastic syndromes.
In order to obtain more insight into the nature of the abnormal in vitro colony formation in myelodysplastic syndromes (MDS), we investigated the kinetics of the colony formation of 23 MDS cases in response to recombinant human interleukin-3 (IL-3), Granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating Factor (G-CSF), and giant cell tumor cell line conditioned medium (GCT-CM). The kinetics of GCT-CM-induced colony formation were comparable to that of G-CSF-induced colony growth, both in MDS and in normal bone marrow cultures. Colony formation was found to be delayed in MDS. The delay in colony formation was most apparent in the GCT-CM (G-CSF) responsive progenitor cell compartment. In MDS cases with clinical features of high risk disease, this delay was more pronounced as compared with low risk cases (7 and 3 days, respectively, in response to GCT-CM). The delay in colony formation was found to be caused by an increase in the time interval before progenitor cells had begun to divide. These results suggest that a prolongation of the time spent in G0 of myeloid progenitor cells in MDS may be the cause of the indolent in vitro colony formation observed in this disease.
Department of Hematology, Cell Biology, and Genetics, Erasmus University Rotterdam, The Netherlands.
M
M
Schipperus
P
P
Sonneveld
J
J
Lindemans
A
A
Hagemeijer
N
N
Vink
J
J
Pegels
J
J
Abels
D001853:Bone Marrow / Q000187:drug effects / Q000502:physiology; D001854:Bone Marrow Cells; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D003470:Culture Media; D003520:Cyclophosphamide / Q000031:analogs & derivatives / Q000494:pharmacology; D005870:Giant Cell Tumors / Q000473:pathology; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured
D003115:Colony-Stimulating Factors; D003470:Culture Media; D006133:Growth Substances; D007377:Interleukin-3; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; C011272:perfosfamide