INHIBITION OF GROWTH AND INDUCTION OF APOPTOSIS BY ALL-TRANS-RETINOICACID IN LYMPHOID-CELL LINES TRANSFECTED WITH THE PML RAR-ALPHA FUSIONGENE/

The interaction of an exogenous PML/RAR alpha fusion gene associated w ith acute promyelocytic leukaemia, with all-trans retinoic acid (ATRA) was examined in two lymphoid cell lines. L1210 and MOLT-4 cells were transfected with PML/RAR alpha cDNA in the expression vector pGD and s table transformants (L1210PML/RAR alpha and MOLT-4PML/RAR alpha) were selected with G418. ATRA inhibited the growth of these stable transfor mants, as assessed by [H-3]thymidine incorporation, in a dose-dependen t manner, but had no effect on the growth of control cells stably tran sformed with neomycin resistant gene alone. ATRA also induced apoptosi s, as assessed by fragmentation of genomic DNA, in L1210PML/RAR alpha and MOLT-4PML/RAR alpha cells but not in control cells. The exogenous PML/RAR alpha fusion gene therefore probably mediates the effects of A TRA on cell growth and apoptosis in these cell lines.