Effects of colony-stimulating factors on the all-trans retinoic acid-induced differentiation of acute promyelocytic leukemic cells.

Abstract

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.

• Authors: H C Hsu, W H Tsai, M L Hsu, C H Ho, S Y Wang
• Journal: Zhonghua yi xue za zhi = Chinese medical journal; Free China ed (Zhonghua Yi Xue Za Zhi (Taipei)) Vol. 57 Issue 2 Pg. 93-9 (Feb 1996) ISSN: 0578-1337 [Print] China (Republic : 1949- )
• PMID: 8634936 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Colony-Stimulating Factors
• Interleukin-3
• Granulocyte Colony-Stimulating Factor
• Tretinoin
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Cell Differentiation (drug effects)
• Colony-Stimulating Factors (pharmacology)
• Granulocyte Colony-Stimulating Factor (pharmacology)
• Granulocyte-Macrophage Colony-Stimulating Factor (pharmacology)
• Humans
• Interleukin-3 (pharmacology)
• Leukemia, Promyelocytic, Acute (pathology)
• Tretinoin (pharmacology)
• Tumor Cells, Cultured (drug effects, pathology)