EFFECTS OF RECOMBINANT HUMAN STEM-CELL FACTOR (RH-SCF) ON COLONY FORMATION AND LONG-TERM BONE-MARROW CULTURES (LTBMC) IN PATIENTS WITH MYELODYSPLASTIC SYNDROMES
D. Soligo et al., EFFECTS OF RECOMBINANT HUMAN STEM-CELL FACTOR (RH-SCF) ON COLONY FORMATION AND LONG-TERM BONE-MARROW CULTURES (LTBMC) IN PATIENTS WITH MYELODYSPLASTIC SYNDROMES, European journal of haematology, 52(1), 1994, pp. 53-60
Stem cell factor (SCF), the ligand of the c-kit receptor, is a potent
enhancing cytokine for haematopoietic cells in the presence of IL-3, G
M-CSF and erythropoietin (Epo). In the clonogenic assays of 63 MDS pat
ients, the addition of rh-SCF + GM-CSF and/or IL-3 induced a significa
nt increase (p < 0.001) in the number and size of CFU-GM. Never reachi
ng the levels of controls, this increase was seen in all FAB subtypes,
but particularly in RA. There was no significant increase in cluster
formation, even in RAEB or RAEBt. Rh-SCF (10 ng/ml) led to mean increa
ses of up to 26 times in the number of Epo-dependent BFU-E colonies, p
articularly in RA (p < 0.001) and RAEB (p < 0.05). Individual response
s varied widely (especially in RA) from no response to supranormal lev
els. Added to the weekly refeed of 37 MDS LTBMC, SCF (10 ng/ml) induce
d only a 7% mean increase in both cell output and the number of clonog
enic cells recovered in the supernatant. Immunohistochemical examinati
on of the supernatant showed significant increases in differentiating
myeloid cells in all examined cases, and in erythroid cells in 3 cases
; blast cells increased in only 3 cases. These data suggest that rh-SC
F is capable of at least partially reversing defective MDS myeloid hae
matopoiesis, and leads no overt risk of leukaemic transformation. Its
potent effect on erythroid cells is encouraging for future clinical ap
plications in patients, particularly if they are selected by means of
in vitro tests.