Study On The Telomere Length, Telomerase Activity And The Correlated Factors In Acute Leukemia

Objective: To examine the telomere length, telomerase activity, the gene expression of human Telomerase Reverse Transcriptase (hTERT) , c-myc and human telomeric-repeat binding facter( TRF1) , and to analyze their correlations in acute leukemia.Methods: The telomerase activity was semi-quantitatively examined in the bone marrow (BM) mononuclears cells (MNCs) of 35 acute leukemia patients and 15 control cases by PCR-ELISA; The mRNA expression of hTERT and c-myc was determined by RT-PCR at the same time. The telomere length of 30 acute leukemia patients and 11 control cases among them was examined by Southern bloting ; The mRNA expression of TRF1 was analyzed by RT-PCR at the same time.Results: The mean expression level of the telomerase activity ,hTERT mRNA and c-myc mRNA in acute leukemia was 0.71± 0.32, 0.47± 0.36 and 0.85 ± 0.31 respectively, which were significantly higher than control cases (p<0.01) .The expression levels of telomeraseactivity and c-myc mRNA had correlations with the expression level of hTERT mRNA.. In the 25 follow-up patients, there was no significant difference on the mean expression levels of the telomerase activity andhTERT mRNA between complete remission cases and none remission cases. The mean expression level of the TRF1 mRNA in acute leukemia was 0.67±0.27,which was significantly higher than the control cases(p<0.01) .The mean telomere length of acute leukemia patients (6.1±1.9Kb) was significantly shorter than that of the control cases(9.5 + 1.4Kb, p<0.01).The patients with short telomere expressed significantly stronger telomerase activity (0.86±0.20) ,than that of the other patients(0.80± 0.27, p<0.01).At the same time, the mean expression level of hTERT and TRF1 in the patients with short telomere (0.56±0.38,0.52±0.24) tend to be higher than that of the other patients (0.31±0.32,0.34±0.26) too(p=0.08, p = 0.06) .Conclusion: 1: The expression of telomerase activity ,hTERT ,c-myc mRNA in acute leukemia was up-regulated. The elevated expression of hTERT may be an important adjuster of telomerase activity. 2: It is likely that c-myc protein has an ability to stimulate the expression of hTERT and thereby enhance telomerase activity, which may be an important step in the leukanogenesis of acute leukemia. 3: There might be a close relationships between the activationiof telomerase and the telomere length in acute leukemia. The mechanism that modulated the telomere length, which might rely on the activation of telomerase was likely to play an important role in the leukanogenesis ofacute leukemia. 4:The suitability down-regulated of TRF1 seemed to be important in the maintenance of the telomere length. 5: The patients with short telomere seemed to need more TRF1 proteins to maintenance the telomere length after the activation of telomerase.