Inhibition of growth and induction of apoptosis by all-trans retinoic acid in lymphoid cell lines transfected with the PML/RARα fusion gene

The interaction of an exogenous PML/RARα fusion gene associated with 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/RARα cDNA in the expression vector pGD and stable transformants (L1210 PML/RAR α and MOLT-4 PML/RAR α) were selected with G418. ATRA inhibited the growth of these stable transformants, as assessed by [³H]thymidine incorporation, in a dose-dependent manner, but had no effect on the growth of control cells stably transformed with neomycin resistant gene alone. ATRA also induced apoptosis, as assessed by fragmentation of genomic DNA, in L1210 PML/RAR α and MOLT-4 PML/RAR α cells but not in control cells. The exogenous PML/RARα fusion gene therefore probably mediates the effects of ATRA on cell growth and apoptosis in these cell lines.