RETINOIDS INCREASE IDARUBICIN CYTOTOXICITY IN HUMAN MYELOID-LEUKEMIA CELL-LINES

All-trans-retinoic acid (ATRA) has proven useful in acute promyelocyti c leukemia (APL). In order to reduce the side effects and to improve t he efficacy of this compound, conventional chemotherapy, and anthracyc lines in particular, are frequently added either during remission indu ction or in consolidation therapy. In this study we aimed at investiga ting the rationale of the combination of ATRA plus idarubicin in two h uman leukemic cell lines, HL-60 and K562, that display a different sen sitivity to ATRA treatment. The effects of ATRA were compared with tho se of two clinically active retinoids, 13-cis-retinoic acid (13-cis-RA ) and 9-cis-retinoic acid (9-cis-RA). Both in HL-60 and in K562 cells, the majority of the combinations of ATRA and idarubicin were synergis tic, while the combinations with 9-cis-RA and 13-cis-RA were more effe ctive in HL-60 and K562 cells, respectively. A 72 h pre-incubation wit h retinoids was able to further increase the cytotoxicity of ATRA plus idarubicin in the two cell lines. Intracellular idarubicin accumulati on was enhanced by retinoids, as demonstrated by a cytofluorimetric me thod. Our results could contribute to provide a rationale for ATRA plu s idarubicin combinations not only in APL but also in acute leukemia o f other cytotypes.