MDS shows a higher expression of hTERT and alternative splice variants in unactivated T-cells

// Wen Dong 1, * , Lei Wu 2, 3, 4, * , Houfang Sun 2, 3, 4 , Xiubao Ren 2, 3, 4 , Pearlie K. Epling-Burnette 5 , Lili Yang 2, 3, 4 1 Department of Orthopaedic Surgery, Tianjin Hongqiao Hospital, Tianjin, P.R. China 2 Department of Immunology, Tianjin Cancer Institute and Hospital, Tianjin Medical University, P.R. China 3 National Clinical Research Center of Cancer, P.R. China 4 Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, P.R. China 5 Immunology Program at the H. Lee Moffitt Cancer Center, Tampa, FL, USA * These authors have contributed equally to this work Correspondence to: Lili Yang, email: yanglili@tjmuch.com Pearlie K. Epling-Burnette, email: Pearlie.Burnette@moffitt.org Keywords: MDS, T-cells, telomerase, hTERT, hTERT alternative splice variants Received: July 27, 2016     Accepted: September 10, 2016     Published: September 19, 2016 ABSTRACT Telomere instability and telomerase reactivation are believed to play an important role in the development of myelodysplastic syndromes (MDS). Abnormal enzymatic activity of human telomerase reverse transcriptase (hTERT), and its alternative splice variants have been reported to account for deregulated telomerase function in many cancers. In this study, we aim to compare the differences in expression of hTERT and hTERT splice variants, as well as telomere length and telomerase activity in unstimulated T-cells between MDS subgroups and healthy controls. Telomere length in MDS cases was significantly shorter than controls (n = 20, p <0.001) and observed across all subtypes of MDS using World Health Organization classification (WHO subgroups versus control: RARS, p = 0.009; RCMD, p =0.0002; RAEB1/2, p =0.004, respectively) and the International Prognostic Scoring System (IPSS subgroups: Low+Int-1, p <0.001; Int-2+High, p =0.004). However, unstimulated T-cells from MDS patients (n=20) had significantly higher telomerase activity ( p =0.002), higher total hTERT mRNA levels ( p =0.001) and hTERT α+β- splice variant expression ( p <0.001) compared to controls. Other hTERT splice variants were lower in expression and not significantly different among cases and controls. Telomerase activity was positively correlated with total hTERT levels in MDS (r=0.58, p =0.007). This data is in sharp contrast to data published previously by our group showing a reduction in telomerase and hTERT mRNA in MDS T-cells after activation. In conclusion, this study provides additional insight into hTERT transcript patterns and activity in peripheral T-cells of MDS patients. Additional studies are necessary to better understand the role of this pathway in MDS development and progression.