Study On The Telomere Length, TRF1, HTERT And Survivin In Myelodysplastic Syndromes

Objective:⑴To evaluate telomere length in patients affected by myelodysplastic syndromes (MDS).⑵To evaluate the expression of TRF1 in patients with MDS and aute leukemia(AL).⑶To detect the expression of human telomerase reverse transcriptase (hTERT) and survivin, and to evaluate their roles in myelodysplastic syndromes (MDS). Methods:⑴Using quantitative fluorescence in situ hybridization and flow cytometry (flow-FISH), we evaluated telomere length in peripheral blood (PB) cells of 7 patients affected by MDS compared with 8 sex- and age-matched controls.⑵Using real-time reverse transcription-polymerase chain reaction, we evaluated the expression of telomere binding protein 1 (TRF1) in the bone marrow (BM) mononuclear cells (MNCs) of 41 MDS patients and 17 AL patients.⑶Using reverse transcription-polymerase chain reaction (RT-PCR), we evaluated the expression of hTERT in the bone marrow (BM) mononuclear cells (MNCs) in 66 patients affected by MDS. Using real-time reverse transcription-polymerase chain reaction (RQ-PCR), we evaluated the expression of survivin in the bone marrow (BM) mononuclear cells (MNCs) of 60 MDS patients. Results:⑴In the healthy controls, we found a significant correlation between telomere length and age (r=0.862, P=0.006). But in the patients affected by myelodysplastic syndromes, we found no correlation between telomere length and age (r=0.232, P=0.616). The mean RTL of telomere length in the patients affected by MDS-RA was 0.742±0.07 and in the healthy controls was 0.871±0.06. There was no significant difference between MDS-RA patients and healthy controls (P=0.066).⑵TRF1 expression was detectable in 41 patients affected by myelodysplastic syndromes, 17 patients affected by acute leukemia and the controls. The expression of TRF1 in MDS patients was significantly higher than the controls(P<0.05=.There was no significant difference between AL patients and the controls(P>0.05).The expression of TRF1 in RA/RARS patients was significantly higher than the controls. With the desease improved, the expression of TRF1 decreased and had no significant difference with the controls. The expression of TRF1 in RAEB/RAEB-t patients was significantly lower than the RA/RARS patients but significantly higher than the controls(P<0.05).⑶The expression of hTERT was significantly elevated in RA/RARS patients as well as RAEB/RAEB-t patients compared with controls(P<0.005).With the disease improved, the expression of hTERT was decreased and had no significant difference compared with the controls (P>0.25).There was no significant difference between IPSS low +int-1 risk group and int-2+high-risk group(P>0.50).The expression of survivin was significantly elevated in RA/RARS patients compared with controls(P<0.02).But there was no significant difference between RAEB/RAEB-t patients and the controls(P>0.05).The expression of survivin in IPSS low+int-1 risk group was significantly higher than the controls(P<0.02), and there was no significant difference between IPSS int-2+high-risk group patients and the controls(P>0.10).And there was no difference between hTERT positive patients and negative patients(P>0.50).Conclusion:⑴The dynamics of telomere in MDS patients was different compared with the normals. The telomere length of MDS patients didn't loss with age.⑵The expression of TRF1 may had an important role in the telomere dynamics of MDS.⑶The expression of hTERT and the decrease of survivin expression, may had a critical role to promote the malignant clone of MDS to escape apoptosis and acquare the ability to divide without control.