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.