G-CSF ACTIVATES STAT PATHWAYS IN KASUMI-1 MYELOID LEUKEMIC-CELLS WITHTHE 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 (rh G-CSF) on the Kasumi-1 AML2 t(8; 21) cell line. Upon incubation with r hG-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. A t that time, more than 80% of the cell population expressed myeloid di fferentiation antigens (CD11b, CD13, CD15 and CDw65), and increased G- CSF receptors. Gel shift assays were performed with nuclear extracts o f 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 supers hift assays to be STAT3/STAT3, STAT1/STAT3 and STAT1/STAT1 dimers. The se results suggest that in G-CSF-sensitive Kasumi-1 cells, normal JAK- STAT pathways are activated, providing a further molecular basis for t he effect of G-CSF in these cells.