DESFERIOXAMINE INCREASES IRON DEPLETION AND APOPTOSIS INDUCED BY ARA-C OF HUMAN MYELOID LEUKEMIC-CELLS

We investigated whether changes in iron metabolism and the transferrin receptor (TRF-R) expression were involved in the antileukaemic effect s of arabinoside cytosine (ara-C). Treatment with 100 nM ara-C for 48 h reduced thymidine uptake and increased the surface expression of the TRF-R on leukaemic blasts derived from 13/16 (81%) patients and on th e HL-60 and U-937 cell lines. Whereas intracellular non-haem iron was strongly depleted 24 h after ara-C addition, TRF-R up-regulation and r ecovery of intracellular non-haem iron concentration occurred together after a longer exposure of the cultured cells to the drug. Since iron is an essential regulator of cell proliferation we have evaluated the effects of the combination between ara-C and the iron chelator desfer ioxamine (DSF) on the growth of HL-60 and U-937 cells. We found that d esferioxamine strongly potentiated the effects of ara-C on leukaemic c ell growth inhibition and apoptosis. This is the first report of a pos itive interaction between ara-C and an iron chelator in terms of antil eukaemic effects.