TELOMERASE ACTIVITY IN ACUTE MYELOGENOUS LEUKEMIA - CLINICAL AND BIOLOGICAL IMPLICATIONS

We examined telomerase activity in myeloid leukaemic cell lines, norma l haemopoietic cells, and leukaemic blasts from acute myelogenous leuk aemia (AML) patients. Normal bone marrow mononuclear (BMNC) cells expr essed low telomerase activity. Higher telomerase activity was detected in 10 myeloid leukaemic cell lines compared to normal BMNC cells. Tre atment with 1,25(OH)(2)D-3, and vitamin D-3 analogues, EB1089 and KH10 60, reduced telomerase activity in vitamin D-3-sensitive HL-60 cells, whereas vitamin D-3 insensitive K562 cells did not change its activity . This down-regulation of telomerase activity by EB1089 was associated with induction of p21 protein. The rank order of telomerase activity was leukaemic CD34(-) cells > leukaemic CD34(+) cells > normal CD34(-) cells > normal CD34(+) cells. Telomerase activity was positive in all of the AML patients tested; however, heterogeneity of telomerase acti vity was found amongst this group. Therefore we compared telomerase ac tivity with clinical response. Unexpectedly, we found that a higher ra te of complete remission was noted in AML patients with higher telomer ase activity. No association between telomerase activity and biologica l parameters including percentage of S-phase, cytotoxicity to cytosine arabinoside and percentage of CD34(+) cells in AML blasts was found. These results suggest that telomerase activity in AML patients is dete cted with high frequency, but is heterogenous. Expression level of tel omerase activity may have a clinical implication in AML patients regar ding clinical response.