G-CSF activates STAT pathways in Kasumi-1 myeloid leukemic cells with the t(8; 21) translocation: basis for potential therapeutic efficacy.
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.
Da Silva
N
N
Laboratoire de Biologie Cellulaire Hématopoïétique, Hôpital Saint-Louis, Paris, France. n.dasilva@chu.sHouis.fr
Meyer-Monard
S
S
Menot
M L
ML
Degos
L
L
Baruchel
A
A
Dombret
H
H
Chomienne
C
C
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
D004268:DNA-Binding Proteins; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D015534:Trans-Activators; D016179:Granulocyte Colony-Stimulating Factor