Quantitative relationship between functionally active telomerase and major telomerase components (hTERT and hTR) in acute leukaemia cells.

Abstract:

:Functionally active telomerase is affected at various steps including transcriptional and post-transcriptional levels of major telomerase components (hTR and human telomerase reverse transcriptase (hTERT)). We therefore developed a rapid and sensitive method to quantify hTERT and its splicing variants as well as the hTR by a Taqman real-time reverse transcriptase-polymerase chain reaction to determine whether their altered expression may contribute to telomere attrition in vivo or not. Fresh leukaemia cells obtained from 38 consecutive patients were used in this study. The enzymatic level of telomerase activity measured by TRAP assay was generally associated with the copy numbers of full-length hTERT+alpha+beta mRNA (P=0.0024), but did not correlate with hTR expression (P=0.6753). In spite of high copy numbers of full-length hTERT mRNA, telomerase activity was low in some cases correlating with low copy numbers of hTR, raising the possibility that alteration of the hTR : hTERT ratio may affect functionally active telomerase activity in vivo. The spliced nonactive hTERT mRNA tends to be lower in patients with high telomerase activity, suggesting that this epiphenomenon may play some role in telomerase regulation. An understanding of the complexities of telomerase gene regulation in biologically heterogeneous leukaemia cells may offer new therapeutic approaches to the treatment of acute leukaemia.

journal_name

Br J Cancer

authors

Ohyashiki JH,Hisatomi H,Nagao K,Honda S,Takaku T,Zhang Y,Sashida G,Ohyashiki K

doi

10.1038/sj.bjc.6602546

subject

Has Abstract

pub_date

2005-05-23 00:00:00

pages

1942-7

issue

10

eissn

0007-0920

issn

1532-1827

pii

6602546

journal_volume

92

pub_type

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