Supression of telomerase activity in HL60 cells after treatment with differentiating agents.

The human promyelocytic leukemic HL60 cells are immortal and as such express high levels of telomerase activity. All-trans retinoic acid (ATRA) and 1 alpha, 25 dihydroxyvitamin D3 (VD3) induce differentiation of HL60 cells into CD11b+ mature granulocytes and monocytes, respectively. We studied telomerase activity after differentiation of HL60 cells. A marked inhibition of the enzyme activity was observed in the differentiated CD11b+ cells after 72-120 h treatment with either differentiating agent. In contrast, the VD3-treated CD11b- HL60 cells, which failed to undergo differentiation and human erythroleukemic cell line K562, exposed to ATRA retained high levels of telomerase activity. This finding suggests, that telomerase activity is repressed as a differentiation-associated event in HL60 cells. Our results provide the first evidence that immortal leukemic cells, like normal human cells, have a telomerase repressing mechanism which can be activated by differentiation and thus lead to the suppression of telomerase activity. This in vitro model may be useful for studies of the mechanisms controlling telomerase activity and in the search for physiological telomerase modulators.