Telomerase activity and the expression of telomerase components in acute myelogenous leukaemia

Authors

  • Dawei XU,

    1. Department of Medicine, Division of Haematology and Infectious Diseases, Department of Clinical Pharmacology and Department of Oncology, Karolinska Hospital, Stockholm, Sweden
    Search for more papers by this author
  • Astrid Gruber,

    1. Department of Medicine, Division of Haematology and Infectious Diseases, Department of Clinical Pharmacology and Department of Oncology, Karolinska Hospital, Stockholm, Sweden
    Search for more papers by this author
  • Curt Peterson,

    1. Department of Medicine, Division of Haematology and Infectious Diseases, Department of Clinical Pharmacology and Department of Oncology, Karolinska Hospital, Stockholm, Sweden
    Search for more papers by this author
  • Pavel Pisa

    1. Department of Medicine, Division of Haematology and Infectious Diseases, Department of Clinical Pharmacology and Department of Oncology, Karolinska Hospital, Stockholm, Sweden
    Search for more papers by this author

Dr DaweiXu Haematological Research Laboratory, L8:03, CMM, Karolinska Hospital, S-171 76 Stockholm, Sweden.

Abstract

In 95 leukaemic cell samples from 66 patients with acute myelogenous leukaemia (AML) (47 de novo and 19 secondary AML) telomerase activity was determined and the expression of the telomerase components: telomerase reverse transcriptase (hTERT), telomerase RNA template (hTR) and telomerase-associated protein (TP1) evaluated by RT-PCR. Compared to peripheral blood mononuclear cells (PBMC) from normal adult 87% (82/95) of patient samples exhibited elevated telomerase activity. hTERT, but not hTR and TP1 expression strongly correlated with the levels of telomerase activity (r = 0.47, P < 0.0001). The levels of telomerase activity were significantly higher at time of relapse or progression than at time of diagnosis (P = 0.003), and correlated to CD34 expression and chromosomal abnormalities of leukaemic cells (P = 0.01 and P = 0.001 respectively). The rate and duration of complete remission (CR) did not correlate with the levels of telomerase activity at diagnosis. Among eight patients in first relapse, however, two of three with low levels of telomerase activity re-entered CR, whereas none of five patients with high telomerase activity achieved a second CR. Taken together, telomerase activation/up-regulation in AML is a disease progression-associated event. Undifferentiated status and chromosomal aberration also lead to the up-regulation of telomerase activity in AML.

Ancillary