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Chin Med J (Taipei) 1996;57:93-9.
1Division of Hematology, Department of Medicine; and 2Department of Medical Research, Veterans General Hospital-Taipei and National Yang-Ming University, Taipei, Taiwan, R.O.C.
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 10-9M of ATRA, but reduced progressively when exposed to ATRA at the concentrations of 10-8M to 10-6M. 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 10-7M 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 (10-9M - 10-6M) 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.
[Chin Med J (Taipei) 1996; 57: 93-9.]
Keywords: ATRA, differentiation, G-CSF, GM-CSF, IL-3
Received: June 16, 1995.
Accepted: October 9, 1995.
Reprint requests to:
Hui-Chi Hsu, M.D.
Division of Hematology
Department of Medicine
Veterans General Hospital-Taipei
201, Sec. 2, Shih-Pai Road
Taipei
Taiwan, R.O.C.
Copyright: 1996, Chinese Medical Association (Taipei)