A study of the relationship between expression level of TRF1 protein and telomerase activity in human acute leukemia

Objective： To study the expression level of TRF1 （telomeric repeat binding factor 1） protein in human acute leukemia and relationship between expression level of TRF1 protein and telomerase, Methods： A quantitative Western±Blot technique was developed using anti±TRF1^33±277 monoclonal antibody and GST±TRFI purity protein as a standard to further determine the expression level of TRF1 protein in total proteins extracted from clinical specimens. Results： Bone marrow tissues of 20 acute leukemia patients were studied, 11 healthy donors＇ bone marrows were taken as a control. The expression level of TRF1 protein was significantly higher （P〈0.01） in normal bone marrow （（2.2174±0.462） μg/μl） than that of acute leukemia patients （（0.7544±0.343） μg/μl）, But there was no remarkable difference between ALL and ANLL patients （（0.6184±0.285） μg/μl vs （0.8454±0.359） μg/μl, P〉0.05）. After chemotherapy, TRFI expression level of patients with complete remission elevated （（0.7724±0.307）/μg/μl vs （1.6834±0,344）μg/μl, P〈0.01 ）, but lower than that of normal （（2.2174±0.462）/μg/μl, P〈0.01）. There was no significantly difference after chemotherapy （（0.7264±0.411） μg/μl vs （0.895±0.339） μg/μl,p〉0.05）. TRF1 expression level of patients with complete remission is higher than that of patients without complete remission （（1,683±0.344）μg/μl vs （0.895±0.339）μg/μl P〈0.01）. All samples were determined for telomerase activity. It was confirmed that the activity of telomerase in normal bone marrow was lower than that of acute leukemia patients （（0.125±0.078） μg/μl vs （0.765±0.284）μg/μl, P〈0.01）. There was no significant difference of expression level ofTRF I protein between ALL and ANLL patients （（0.897±0.290） μg/μl vs （0.677±0.268） μg/μl, P〉0.05）. After chemotherapy, telomerase activity of patients with complete remission decreased （（0.393±0.125） μg/μl）, but was still higher than that of normal （（0.125±0.078） μg/μl, P〈0.01）. Conclusion： The expression level of TRF1 protein has correlativity to the activity of telomerase （P〈0.001）.

How will telomeric complex be further contributed to our longevity?—The potential novel biomarkers of telomere complex counteracting both aging and cancer

With the smooth move towards the coming expected clinical reports of anticancer pharmaceutical molecules targeting telomeres and telomerase,and also with the exciting success in the extension of lifespan by regulating telomerase activity without increased onset of oncogenesis in laboratory mouse models(Garcia-Cao et al.,2006;Jaskelioff et al.,2011),we are convinced that targeting telomeres based on telomerase will be a potential approach to conquer both aging and cancer and the idea of longevity seems to be no more mysterious.More interestingly,emerging evidences from clinical research reveal that other telomeric factors,like specifi c telomeric binding proteins and nonspecific telomere associated proteins also show crucial importance in aging and oncogenesis.This stems from their roles in the stability of telomere structure and in the inhibition of DNA damage response at telomeres.Uncapping these proteins from chromosome ends leads to dramatic telomere loss and telomere dysfunction which is more abrupt than those induced by telomerase inactivation.Abnormal expression of these factors results in developmental failure,aging and even oncogenesis evidenced by several experimental models and clinical cases,indicating telomere specifi c proteins and its associated proteins have complimentary roles to telomerase in telomere protection and controlling cellular fate.Thus,these telomeric factors might be potential clinical biomarkers for early detection or even therapeutic targets of aging and cancer.Future studies to elucidate how these proteins function in telomere protection might benefit patients suffering aging or cancer who are not sensitive to telomerase mediation.