Induction of differentiation of retinoic acid-resistant acute promyelocytic leukemia cells by the combination of all-trans retinoic acid and granulocyte colony-stimulating factor.
An acute promyelocytic leukemia (APL) cell line with natural resistance to all-trans retinoic acid (ATRA), UF-1, was induced to differentiate into mature granulocyte when treated with the combination of ATRA and granulocyte colony-stimulating factor (G-CSF), while neither of them alone was capable of inducing the differentiation effectively. Continuous presence of both agents was required for the maximal differentiation-inductive effect. Neither proliferation arrest nor induction of apoptosis preceded the differentiation. Differentiated phenotype was accompanied by growth arrest, however, not by increased apoptosis. It was assumed that cellular events at the downstream of the signaling pathways of ATRA and G-CSF cooperatively played pivotal roles in the differentiation-induction.
Higuchi
Takakazu
T
Division of Hematology, Internal Medicine, Showa University Fujigaoka Hospital, 1-30 Fujigaoka, Aoba-ku, Yokohama 227-8501, Japan. thiguchi@med.showa-u.ac.jp
Kizaki
Masahiro
M
Omine
Mitsuhiro
M
D017209:Apoptosis / Q000187:drug effects; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000473:pathology*; D010766:Phosphorylation; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D014212:Tretinoin / Q000008:administration & dosage / Q000494:pharmacology*; D014443:Tyrosine / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; C070790:CEBPE protein, human; D016179:Granulocyte Colony-Stimulating Factor; D014443:Tyrosine; D014212:Tretinoin