Retrovirus-mediated gene transfer of granulocyte colony-stimulating factorreceptor (G-CSFR) cDNA into MDS cells and induction of their differentiation by G-CSF
S. Nakamura et al., Retrovirus-mediated gene transfer of granulocyte colony-stimulating factorreceptor (G-CSFR) cDNA into MDS cells and induction of their differentiation by G-CSF, CYTOK CELL, 6(2), 2000, pp. 61-70
Myelodysplastic syndromes (MDS) are clonal disorders in which the proper di
fferentiation of hematopoietic stem cells is impaired. There is no effectiv
e 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 trie
d retroviral transduction of granulocyte colony-stimulating factor receptor
(G-CSFR) into an interleukin-3-dependent MDS cell line, MDS-L, since expre
ssion of G-CSFR is known to be essential for the differentiation of myeloid
progenitor cells and this expression is impaired in most MDS cells. Ectopi
c expression of human G-CSFR cDNA in NIDs-L cells gave rise to granulocytic
differentiation by G-CSF stimulation. G-CSF caused the transformants expre
ssing G-CSFR to display a morphological characteristic of mature granulocyt
es, upregulated CD11b on the cell surface, and improved NET reduction activ
ity. These results demonstrate that MDS-L cells ecopically expressing G-CSF
R are induced to granulocytic differentiation upon exposure to G-CSF, and s
hed light on the molecular mechanisms of maturation arrest in MDS cells.