Abstract
Objective:As evidence was shown that abnormal shortening of telomeres begins to accumulate in myelodysplastic syndrome (MDS) patients, this study was conducted to determine the relationship between the mRNA expression levels of telomere-binding proteins (TRF1/TRF2/TIN2/TPP1/POT1/RAP1) and the risk level in MDS.Materials and Methods:There were 40 patients with MDS and 40 normal controls in this study. Methods including telomere content assays and quantitative reverse transcription-polymerase chain reaction were used to examine the mRNA levels of TRF1/TRF2/TIN2/TPP1/POT1/RAP1 in patients with MDS.Results:Compared to the normal group used as a control, the mRNA expression levels of RAP1/POT1/TPP1 of the patients with MDS were decreased, whereas their levels of TRF1/TRF2 and TIN2 were increased. A positive correlation was found between the TRF1, TRF2, and TIN2 mRNA expression levels and the risk level of the International Prognostic Scoring System (IPSS) and the World Health Organization Prognostic Scoring System (WPSS) criteria; however, a negative correlation was found between RAP1/POT1/TPP1 mRNA expression levels and the risk levels of IPSS and WPSS criteria.Conclusion:Because the reduction of TRF1/TRF2/TIN2 mRNA expression and the increase of RAP1/POT1/TPP1 mRNA expression are closely related to the risk levels of the IPSS and WPSS criteria in MDS, it is thought that these telomere-binding proteins could lead to abnormal telomere length and function, which cause chromosomal abnormalities in MDS. With this evidence, we suggest that those proteins’ mRNA expressions could be used as biomarkers for the assessment of the risk degree of MDS patients.
Highlights
Chromosome stability is controlled by telomeres, which are regions of repetitive DNA sequences (TTAGGG) at the end of each chromosome regulating end-to-end fusions and recombination
Because the reduction of telomere repeat factor-1 (TRF1)/TRF2/TRF1-interacting protein 2 (TIN2) mRNA expression and the increase of RAP1/protection of telomeres-1 (POT1)/TPP1 mRNA expression are closely related to the risk levels of the International Prognostic Scoring System (IPSS) and World Health Organization Prognostic Scoring System (WPSS) criteria in myelodysplastic syndrome (MDS), it is thought that these telomere-binding proteins could lead to abnormal telomere length and function, which cause chromosomal abnormalities in MDS
Patients were divided into cases of refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory cytopenias with multilineage dysplasia (RCMD), refractory anemia with excess blasts-1 (RAEB-1), and refractory anemia with excess blasts-2 (RAEB-2) based on the 2008 World Health Organization (WHO) diagnosis and classification schemes
Summary
Chromosome stability is controlled by telomeres, which are regions of repetitive DNA sequences (TTAGGG) at the end of each chromosome regulating end-to-end fusions and recombination. Shelterin, which can regulate telomere length and protect telomere function, is an important protein-binding complex composed of telomere repeat factor-1 (TRF1) and -2 (TRF2), protection of telomeres-1 (POT1), TRF2-interacting telomeric protein (RAP1), TRF1-interacting protein 2 (TIN2), and TIN2organizing protein (TPP1). There are some similarities between TRF1 and TRF2, including their sequence and organization, and they and POT1 can influence the telomeric DNA. Our goal was to use reverse transcriptionpolymerase chain reaction (RT-PCR) to detect the mRNA levels of telomere-binding proteins TRF1, TRF2, TIN2, TPP1, POT1, and RAP1 in MDS. We tried to determine whether there were any relationships between the mRNA levels and the International Prognostic Scoring System (IPSS) and World Health Organization Prognostic Scoring System (WPSS) scores of patients with MDS
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