Human recombinant stem cell factor stimulates in vitro proliferation of acute myeloid leukemia cells and expands the clonogenic cell pool.
Stem cell factor (SCF) is a new growth factor acting on early hematopoietic progenitor and stem cells. In our experiments human recombinant SCF stimulated short-term proliferation of accessory cell-depleted acute myeloid leukemia (AML) cells in 13/14 cases, as determined by 3H-thymidine (3H-TdR) incorporation and cell counts. Stimulatory activity was significantly greater than in the presence of GM-CSF and was comparable to that of granulocyte colony-stimulating factor (G-CSF), interleukin 3 (IL-3), and 5637 cell line supernatant (SN). Conversely, the ability of SCF to induce primary colony formation by AML clonogenic cells (CFU-L) was lower than that of granulocyte-macrophage colony-stimulating factor (GM-CSF) and 5637 SN in all but four cases. However, SCF potentiated the stimulatory effect of GM-CSF, G-CSF, and IL-3 on both 3H-TdR incorporation and colony formation. In a 7-day liquid culture SCF enhanced CFU-L recovery in all cases to a significantly greater extent than the other growth factors. A further increment was obtained by combinations of SCF with GM-CSF, G-CSF, or IL-3, and this was significantly more effective than 5637 SN. SCF did not induce leukemic cell differentiation. Human recombinant SCF is therefore highly efficient in stimulating AML cell proliferation and expanding the CFU-L pool. It was not, however, able to support long-term growth of AML cells (beyond 2-7 weeks) in five cases tested.
Carlesso
N
N
Dipartimento di Medicina e Oncologia Sperimentale, Università di Torino, Italia.
Pregno
P
P
Bresso
P
P
Gallo
E
E
Pileri
A
A
Zsebo
K M
KM
Ferrero
D
D
D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000473:pathology*; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D014407:Tumor Cells, Cultured
D015214:Antigens, Differentiation, Myelomonocytic; D003470:Culture Media; D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor