Effects of recombinant human granulocyte colony stimulating factor and granulocyte-monocyte colony stimulating factor on in vitro hemopoiesis in the myelodysplastic syndromes.
We evaluated the effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) and granulocyte-monocyte colony stimulating factor (rhGM-CSF) on the in vitro proliferative, differentiative, and regenerative responsiveness of marrow cells from myelodysplastic syndrome patients (MDS) in comparison to those from normal individuals. Our studies showed decreased primary clonogenicity of myeloid (CFU-GM) and erythroid (BFU-E) hemopoietic progenitor cells from the MDS patients. rhGM-CSF had more potent stimulatory effects than rhG-CSF for MDS marrow CFU-GM growth; no enhanced cellular proliferation in the MDS patients was observed in liquid culture with either rhGM-CSF or rhG-CSF. Decreased myeloid clonal cell self-generation and/or recruitment occurred in the MDS patients upon exposure to either rhG-CSF or rhGM-CSF. rhG-CSF demonstrated more potent granulocytic differentiation effects than rhGM-CSF both for normals and MDS patients using marrow enriched for immature myeloid cells with lesser differentiation noted for MDS. Cytogenetic abnormalities, present with or without additional normal karyotypes in native marrow of four MDS patients, persisted after culture with rhG-CSF, indicating induced differentiation of both normal and abnormal clones. Although proliferative and differentiative effects were seen with both factors these data show MDS marrow cells in vitro to have predominantly differentiative responsiveness to rhG-CSF and proliferative responsiveness to rhGM-CSF.
Department of Medicine, Stanford University Medical Center, California.
A
A
Nagler
N
N
Ginzton
R
R
Negrin
D
D
Bang
T
T
Donlon
P
P
Greenberg
D000328:Adult; D000368:Aged; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000503:physiopathology*; D011994:Recombinant Proteins / Q000494:pharmacology
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor