THE SYNERGISTIC EFFECT OF SIMULTANEOUS ADDITION OF RETINOIC ACID AND VITAMIN-D-3 ON THE IN-VITRO DIFFERENTIATION OF HUMAN PROMYELOCYTIC LEUKEMIA-CELL LINES COULD BE EFFICIENTLY TRANSPOSED IN-VIVO

Both human cell lines HL-60 and AML-193 exhibit a myeloblastic and pro myelocytic morphology, respectively, but may be regarded as bipotent l eukemic precursors. They can be triggered to differentiate to either g ranulocytes or monocytes upon retinoic acid (RA) or 1,25-dihydroxyvita min D (D-3) addition, respectively. We have investigated the effect of combined addition of these chemical inducers on the in-vitro differen tiation of both cell lines. RA and D-3 added together exert synergisti c effects on the in-vitro maturation of these myeloid cell lines. Inte restingly, the additive effects were lost if the cells were incubated with the inducers added at sequential times. The synergistic effect co uld be transposed in vivo and could be clinically significant in the t reatment of the promyelocytic leukemia. This clinical strategy may hel p to prevent retinoic acid resistance or to overcome it in patients re lapsed after RA therapy and usually unresponsive to a reinduction ther apy with RA alone.