The Significance Of Telomerase Activity Detection In The Drug Resistant And Previously Untreated Patients With Acute Leukemia

Telomere is a special structure at the end of the chromosome of the eukaryotic cells. For normal cells, the lengths of telomeres will become shorter and shorter gradually. The telomere length and stability decides the life of the cell,which is closely related with the aging and malignant change. Telomerase is a compound of RNA and protein and a special kind of DNA polymerase. It can use its own RNA as the template to form new terminal repeat sequence and extend telomeres. Recent study has showed telomeres activation is necessary for the immortalized cells and the immortalization is the necessary step for the malignant change. Telomere activity(TA) may take part in the pathogenesis of AL, therefore this retrospective study want to discuss the relationship of TA and drug-resistance in the bone marrow of the AL patients by observing the changes of TA levels. Previously untreated and refractory / resistant AML and ALL patients from September 2005 to March 2008 in our hospital were chosen for the study, with systematically observing the changes of TA in the bone marrow, before/after initial treatment,the treatment after 2 and 3 months. Before treatment, all patients were diagnosed as AL according to the diagnostic criteria and each one must accept the TA test of the bone marrow before/immediately after the initial treatment, 2 and 3 months after the treatment. Empirical therapeutic regimen be adopted by newly diagnosed AL patients (including the remission induction and consolidation) and refractory / resistant AL patients were treated after sensitivity test in vitro. To measure the TA level at each time point during the course of treatment. X2 and t-test for data statistical analysis. For the repeated measurements of the variables we used repeated measurements analysis of variance methods EC statistics. Conclusions: 1. Telomerase is closely related to the outcome and prognosis for AL patients and AML is more representative than ALL. 2. High level of TA before treatment showed poor treatment effect. 3. High level of TA before treatment indicated early recurrence, and the significance of detecting the TA immediately after treatment is much higher than that of before treatment for early recurrence. 4. For refractory/ resistant AML, the patients with high level TA had very poor prognosis. 5. For the previously untreated and refractory / resistant AML patients, the higher is TA before treatment,the shorter is DFS and OS. TA level with recurrence and disease progression was significantly higher than the time of diagnosis and in patients with CR decreased significantly. The level of TA showed normal in the patients with CR. The expression of TA varies with the change of the patients'situation, which suggested dynamic monitoring of TA for AL patients can judge the malignant degree, monitor the progression, predict early recurrence. Therefore, from a theoretical point of view, inhibiting telomerase can inhibit the tumor cell growth. Because most normal tissues and cells did not express TA, to inhibit telomerase can have a minimal impact on the body. In one word, telomerase inhibitor is the ideal target for the anti-neoplasm therapy.