Effect And Mechanism Of IFN-? On Telomere Length In Peripheral Blood Cells Of Patients With Myeloproliferative Neoplasm

Purpose Telomeres are the ends of eukaryotic organisms with linear chromosomes,consisting of a repetitive DNA sequence(TTAGGG)that binds to specific proteins.They protect chromosomal ends from being recognized as DNA breaks,while also preventing loss of genomic information through progressive chromosome shortening caused by the semi-conservative replication of DNA.It was believed that the telomere length of the cell is the genetic property of the cell itself.However,recent studies have shown that cytokines act as "messengers" for communication among cells,and they can be involved in the regulation of telomere length and telomerase activity at the transcriptional level by activating protein kinases and transcription factors.Interferon is the most commonly used cytokine in clinic and can be used to treat myeloproliferative diseases.This study aims to illustrate the effect of IFN-? on telomere length in peripheral blood mononuclear cells in patients by examining the changes in telomere length in peripheral blood mononuclear cells in patients with polycythemia vera and essential thrombocythemia before and after treatment with IFN-?,and the correlation between telomere length and the cumulative therapeutic dose of IFN-?.In addition,through detecting the expression of telomerase reverse transcriptase gene,protection of telomeres 1 gene and ataxia telangiectasia mutated and Rad3 related gene,it investigates the potential mechanism of IFN-? on the telomere length of PBMCs.Methods The subjects were all diagnosed with polycythemia vera and essential thrombocythemia from April to December 2017 in Tianjin Medical University General Hospital,whose diagnostic criteria were in accordance with the Chinese expert consensus on the evaluation and treatment of polycythemia vera(2016 edition)and essential thrombocytosis(2016 edition).There were 24 patients who had received IFN-? therapy and 24 patients who had no treatment,and there was no statistical difference in gender and age between the two groups.PBMCs were extracted from all subjects,and the relative telomere length and the expression of h TERT gene,POT1 gene,and ATR gene in PBMCs from patients with PV and ET were measured by real-time quantitative polymerase chain reaction.The cumulative therapeutic dose of IFN-? in patients with PV and ET was calculated,and the relationship between relative telomere length and it was studied.All the results were analyzed with the statistical software SPSS24.0.Since the experimental data were in accordance with the skewed distribution,we used the Mann-Whitney U test to compare the mean values between the two groups and expressed them in the median and the lower and upper quartiles,and recorded them as M(P25-P75).The correlation analysis was performed using the Spearman method.Results Part ?The relative telomere length of PBMCs in the IFN-? treated group0.277(0.105~0.714)was significantly shorter than that in the untreated group0.625(0.297~1.824)(P=0.016*).The relative telomere length of PBMCs in the IFN-? treated group was significantly negatively correlated with the cumulative therapeutic dose of IFN-?(r=-0.533,P=0.015*).Part ?The expression level of h TERT m RNA in PBMCs of IFN-? treated group 0.024(0.005~0.120)was significantly lower than that of the untreated group 0.122(0.068~0.441)(P=0.005**).The expression level of POT1 m RNA in PBMCs of IFN-? treated group 0.078(0.014~3.905)was lower than that of the untreated group 2.690(0.139~13.313)(P=0.027*).The expression level of ATR m RNA in PBMCs of IFN-? treated group 0.043(0.023~0.739)was higher than that of the untreated group 0.021(0.011~0.055)(P=0.038*).Conclusions1.The relative telomere length of PBMCs after treatment with IFN-? in patients with PV and ET was significantly shorter than those without IFN-? treatment,and the relative telomere length was significantly negatively correlated with the cumulative therapeutic dose of IFN-?.2.The expressions of h TERT gene and POT1 gene in PBMCs of patients with PV and ET were decreased after IFN-? treatment,but the expression of ATR gene was increased.This is possibly an important path for IFN-? to cause telomere shortening and apoptosis.