title: G-CSF activates STAT pathways in Kasumi-1 myeloid leukemic cells with the t(8; 21) translocation: basis for potential therapeutic efficacy.
abstract: In an attempt to find new agents that promote differentiation and have therapeutic potential in acute myeloid leukemias, we have studied the effect of recombinant human granulocyte colony stimulating factor (rhG-CSF) on the Kasumi-1 AML2 t(8; 21) cell line. Upon incubation with rhG-CSF (0.2-2000 ng/ml), Kasumi-1 cells showed a peak of cell growth, with a subsequent decrease of cell survival after 4 days of culture. At that time, more than 80% of the cell population expressed myeloid differentiation antigens (CD11b, CD13, CD15 and CDw85), and increased G-CSF receptors. Gel shift assays were performed with nuclear extracts of Kasumi-1 cells after 1, 5, 10, 15, 30 and 60 min incubations with G-CSF and oligonucleotides containing the high-affinity SIF-binding site. At least three specific complexes were obtained, and shown by supershift assays to be STAT3/STAT3, STAT1/STAT3 and STAT1/STAT1 dimers. These results suggest that in G-CSF-sensitive Kasumi-1 cells, normal JAK-STAT pathways are activated, providing a further molecular basis for the effect of G-CSF in these cells.
authors.affiliation: Laboratoire de Biologie Cellulaire Hématopoïétique, Hôpital Saint-Louis, Paris, France. n.dasilva@chu.sHouis.fr
authors.forename: N
authors.initials: N
authors.lastname: Da Silva
authors.forename: S
authors.initials: S
authors.lastname: Meyer-Monard
authors.forename: M L
authors.initials: ML
authors.lastname: Menot
authors.forename: L
authors.initials: L
authors.lastname: Degos
authors.forename: A
authors.initials: A
authors.lastname: Baruchel
authors.forename: H
authors.initials: H
authors.lastname: Dombret
authors.forename: C
authors.initials: C
authors.lastname: Chomienne
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D015534:Trans-Activators; D016179:Granulocyte Colony-Stimulating Factor