Telomerase activity in acute myelogenous leukaemia: clinical and biological implications

Authors

  • Jae Goo Seol,

    1. Cancer Research Centre, Division of Haematology/Oncology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul,
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  • Eun Shil Kim,

    1. Cancer Research Centre, Division of Haematology/Oncology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul,
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  • Woo Hyun Park,

    1. Cancer Research Centre, Division of Haematology/Oncology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul,
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  • Chul Won Jung,

    1. Division of Haematology/Oncology, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul,
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  • Byoung Kook Kim,

    1. Cancer Research Centre, Division of Haematology/Oncology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul,
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  • Young Yiul Lee

    1. Division of Haematology/Oncology, Department of Internal Medicine, Han Yang University College of Medicine, Seoul, Korea
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Dr Young Yiul Lee Division of Haematology/Oncology, Department of Internal Medicine, Han Yang University Hospital, 17 Haeng Dang-dong, Sung Dong-ku, Seoul 133-792, South Korea.

Abstract

We examined telomerase activity in myeloid leukaemic cell lines, normal haemopoietic cells, and leukaemic blasts from acute myelogenous leukaemia (AML) patients. Normal bone marrow mononuclear (BMNC) cells expressed low telomerase activity. Higher telomerase activity was detected in 10 myeloid leukaemic cell lines compared to normal BMNC cells. Treatment with 1,25(OH)2D3, and vitamin D3 analogues, EB1089 and KH1060, reduced telomerase activity in vitamin D3-sensitive HL-60 cells, whereas vitamin D3 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 activity was found amongst this group. Therefore we compared telomerase activity with clinical response. Unexpectedly, we found that a higher rate of complete remission was noted in AML patients with higher telomerase activity. No association between telomerase activity and biological 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 detected with high frequency, but is heterogenous. Expression level of telomerase activity may have a clinical implication in AML patients regarding clinical response.

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