Retrovirus-mediated gene transfer of granulocyte colony-stimulating factor receptor (G-CSFR) cDNA into MDS cells and induction of their differentiation by G-CSF.
Myelodysplastic syndromes (MDS) are clonal disorders in which the proper differentiation of hematopoietic stem cells is impaired. There is no effective treatment for this stem cell disorder at present. In an attempt to find a new strategy that promotes the differentiation of MDS blast cells, we tried retroviral transduction of granulocyte colony-stimulating factor receptor (G-CSFR) into an interleukin-3-dependent MDS cell line, MDS-L, since expression of G-CSFR is known to be essential for the differentiation of myeloid progenitor cells and this expression is impaired in most MDS cells. Ectopic expression of human G-CSFR cDNA in MDS-L cells gave rise to granulocytic differentiation by G-CSF stimulation. G-CSF caused the transformants expressing G-CSFR to display a morphological characteristic of mature granulocytes, upregulated CD11b on the cell surface, and improved NBT reduction activity. These results demonstrate that MDS-L cells ecopically expressing G-CSFR are induced to granulocytic differentiation upon exposure to G-CSF, and shed light on the molecular mechanisms of maturation arrest in MDS cells.
Nakamura
S
S
Department of Internal Medicine III, Hamamatsu University School of Medicine, Japan. satoki@hama-med.ac.jp
Ohnishi
K
K
Yoshida
H
H
Shinjo
K
K
Takeshita
A
A
Tohyama
K
K
Ohno
R
R
Koide
Y
Y
D015703:Antigens, CD / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D018076:DNA, Complementary; D005822:Genetic Vectors; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects; D049452:Green Fluorescent Proteins; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D008164:Luminescent Proteins / Q000235:genetics; D016177:Macrophage-1 Antigen / Q000032:analysis; D009190:Myelodysplastic Syndromes / Q000473:pathology*; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D012190:Retroviridae; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014162:Transfection / Q000379:methods*
D015703:Antigens, CD; D018076:DNA, Complementary; D007377:Interleukin-3; D008164:Luminescent Proteins; D016177:Macrophage-1 Antigen; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D049452:Green Fluorescent Proteins; D004247:DNA; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine