Improved Antileukemic Activity of the Combination of Ara-C with GM-CSF and IL-3 Fusion Protein (PIXY321)

Co-treatment with GM-CSF/IL3 fusion protein pIXY321 significantly increased apoptosis and the loss of clonogenic survival of HL-60 cells due to a treatment with high dose Ara-C (100 μM) for 4 hours or prolonged treatment with lose dose Ara-C (10 nM) for 5 days. In contrast, pIXY321 inhibited high dose Ara-C-in-duced apoptosis in CD34+ normal bone marrow cells. Combined treatment with staurosporine also enhanced Ara-C induced apoptosis in HL-60 cells. None of these modulations of Ara-C-induced apoptosis in the leukemic or normal cells was associated with appreciable alterations in intracellular p26BCL-2 levels.