Effects of colony-stimulating factors on the all-trans retinoic acid-induced differentiation of acute promyelocytic leukemic cells.
BACKGROUND
NB4, a cell line derived from a patient with t(15;17) acute promyelocytic leukemia (APL) that undergoes granulocytic differentiation when treated with pharmacological doses of all-trans retinoic acid (ATRA), was used as a model for induction of differentiation. In this study, we examined the interaction of colony-stimulating factors (CSF) and ATRA in affecting the proliferation and differentiation of NB4 cells.


METHODS
Nitroblue tetrazolium (NBT) reduction was used as a functional marker of leukemia cell differentiation. The number of viable cells was counted by trypan blue exclusion test.


RESULTS
Proliferation of NB4 cells increased when exposed to 10(-9)M of ATRA, but reduced progressively when exposed to ATRA at the concentrations of 10(-8)M to 10(-6)M. After culture for 5 days, NBT-positive cell was not detectable in the control cultures with medium alone, but its percentage apparently increased to 84% at 10(-7)M ATRA. Granulocyte (G)-CSF per se had no effect on the granulocytic differentiation of NB4 cells, but it could enhance the NBT reduction when used in combination with various concentrations (10(-9)M -10(-6)M) of ATRA. Interleukin (IL)-3 or granulocyte-macrophage-CSF (GM-CSF) alone also had no effect on the NBT reduction in NB4 cells. However, when combined with ATRA, both caused a slight suppression of NBT reduction. No synergistic effect was noted between IL-3 and G-CSF on the ATRA-induced granulocytic differentiation.


CONCLUSIONS
G-CSF, but not IL-3 or GM-CSF, can enhance the differentiating activity of ATRA. Further investigations are necessary to evaluate its clinical use.
Hsu
H C
HC
Department of Medicine, Veterans General Hospital-Taipei, Taiwan, R.O.C.
Tsai
W H
WH
Hsu
M L
ML
Ho
C H
CH
Wang
S Y
SY
D002454:Cell Differentiation / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D003115:Colony-Stimulating Factors; D007377:Interleukin-3; D016179:Granulocyte Colony-Stimulating Factor; D014212:Tretinoin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor