Gamma-irradiation does not impair ATRA-induced maturation of myeloid leukaemic cells: implication for combined radiation and differentiation therapy

In the present study we investigated the effects of various doses of γ-irradiation, followed by induction of granulocytic differentiation with all-trans-retinoic acid (ATRA), on proliferative rate, differentiation capability and oxidative metabolism of leukaemic cells from two different myeloid leukaemia cell lines, HL-60 and PLB-985. Regarding the effects of such combined treatment on the proliferative capabilities of HL-60 and PLB-985 cell lines, we showed that their growth kinetics were similar after 2 Gy γ-irradiation combined with ATRA. However, with doses >2 Gy, the behaviour of the cell lines differed largely. Indeed, HL-60 appeared to be more radiosensitive than PLB-985 regarding cell viability and proliferation. Besides, whatever dose of irradiation (2, 5 or 10 Gy) was applied, ATRA was still able to induce differentiation of HL-60 and PLB-985 into granulocytes that retained the capacity to produce superoxide anion. The results of these in vitro studies suggest that leukaemia cell lines retain their ability to respond to ATRA, a granulocytic-differentiating inducer following high doses of irradiation. This may have implications for the use of radiation therapy in combination with ATRA for the treat-ment of extramedullary infiltrations of myeloid leukaemias in humans.