Granulocyte-colony stimulating factor and retinoic acid cooperatively induce granulocyte differentiation of acute promyelocytic leukemia cells in vitro.
The interaction of granulocyte-colony stimulating factor (G-CSF) and retinoic acid (RA) in proliferation and differentiation of acute promyelocytic leukemia (APL) cells was examined. G-CSF stimulated proliferation of APL cells at concentrations of 0.1 to 50 ng/ml in a dose dependent manner. More than 10(-8) M RA induced granulocytic differentiation of APL cells. Although G-CSF induced lysozyme activities in APL cells, it alone did not induce terminal differentiation of APL cells. G-CSF significantly enhanced the RA-induced granulocytic differentiation of APL cells in vitro. Enhancement by G-CSF was not due to the prolongation of survival of RA-induced differentiated cells, but the differentiation-inducing effects of G-CSF might be evident only in the presence of RA. Since G-CSF has a potential to induce the granulocytic differentiation of myeloid leukemia cells, G-CSF in combination with RA may be applicable in differentiation induction therapy for some types of myeloid leukemia.
Nakamaki
T
T
Department of Hematology, Showa University School of Medicine, Tokyo.
Sakashita
A
A
Sano
M
M
Hino
K
K
Suzuki
K
K
Tomoyasu
S
S
Tsuruoka
N
N
Honma
Y
Y
Hozumi
M
M
D000328:Adult; D000368:Aged; D000954:Antigens, Surface / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor; D006098:Granulocytes / Q000473:pathology*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D013936:Thymidine / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface; D003115:Colony-Stimulating Factors; D016179:Granulocyte Colony-Stimulating Factor; D014212:Tretinoin; D013936:Thymidine