Impaired response of myelodysplastic marrow progenitors to stimulation with recombinant haemopoietic growth factors.
The regulation of haemopoiesis in myelodysplastic syndromes (MDS) was evaluated by measuring and comparing the in vitro response of marrow progenitors from 18 MDS patients to stimulation with recombinant haemopoietic growth factors (HGFs), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF) and interleukin-3 (IL-3). A similar pattern of colony growth was detected with all three HGFs in most MDS patients, exhibiting subnormal growth of GM-CFU and markedly poor to absent growth of BFU-E and CFU-GEMM. A common severe impairment in the growth of all colony types with all three HGFs was observed in five patients, four of whom presented with pancytopenia. The stimulation of MDS marrow progenitors with a five-fold higher than control saturating dose of HGFs induced a significant increase in the frequency of one, two, or all three colony types in cultures of 14 patients, whereas colony numbers in control (n = 8) marrow cell cultures were not significantly changed. All four of the non-responders were pancytopenic and three exhibited markedly impaired colony growth. Supersaturating GM-CSF, G-CSF and IL-3 increased GM-CFU numbers in six, three, and three patients, respectively. The values for BFU-E were three, six, and seven and for CFU-GEMM two, one, and five. The enhancement of MDS marrow colony numbers by supersaturating HGFs which exert their effects directly or via the action of marrow accessory cells, suggests that the progenitor cell growth abnormalities in these disorders may involve a defect in the capacity of accessory and/or progenitor cells to respond to stimulation with specific haemopoietic growth regulators.
Merchav
S
S
Department of Hematology, Technion Faculty of Medicine, Haifa, Israel.
Wagemaker
G
G
Souza
L M
LM
Tatarsky
I
I
D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical
D007377:Interleukin-3; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor