DIFFERENTIATING EFFECT OF THALIDOMIDE AND GM-CSF COMBINATION ON HL-60 ACUTE PROMYELOCYTIC LEUKEMIA CELLS
A.U. Ural1, 2, , F. Avcu1, 2, M. Zerman3,
M.I. Yilmaz3, A. Pekel4, M. Beyzadeoglu5
1Department of Hematology, Gulhane Military Medical Academy, Ankara, Turkey 2Medical Research Center, Gulhane Military Medical Academy, Ankara, Turkey 3Department of Internal Medicine, Gulhane Military Medical Academy, Ankara, Turkey 4Department of Immunology, Gulhane Military Medical Academy, Ankara, Turkey 5Department of Radiation Oncology, Gulhane Military Medical Academy, Ankara, Turkey
Abstract. Aim: To investigate whether granulocyte-macrophage
colony-stimulating factor (GM-CSF) with or without thalidomide can induce apoptosis and
differentiation of HL-60 acute promyelocytic leukemia cell line in vitro.
Methods: Effect of GM-CSF and thalidomide on proliferation of HL-60 cells was
evaluated by MTT assay, cell cycle analysis was performed by propidium iodide staining
approach and flow cytometry, and apoptosis rate was analyzed using FITC-conjugated
annexin-V and FACScan flow cytometry. Results: The study revealed that thalidomide
alone at high concentrations inhibited HL-60 cell growth and induced apoptosis. Three days
treatment of low-dose thalidomide in combination with GM-CSF induced marked terminal
differentiation of HL-60 cells, as it was assessed by increased expression of
differentiation antigens on cell surface. Conclusion: Treatment of HL-60 cells by
low concentration of thalidomide combined with GM-CSF induced terminal differentiation of
HL60 cells in vitro, which may be advantageous for the elaboration of novel
therapeutic regimens in patients with differentiation-inducible leukemias.