Oncotarget

Research Papers:

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

Wen Dong, Lei Wu, Houfang Sun, Xiubao Ren, Pearlie K. Epling-Burnette and Lili Yang _

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Oncotarget. 2016; 7:71904-71914. https://doi.org/10.18632/oncotarget.12115

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Abstract

Wen Dong1,*, Lei Wu2,3,4,*, Houfang Sun2,3,4, Xiubao Ren2,3,4, Pearlie K. Epling-Burnette5, Lili Yang2,3,4

1Department of Orthopaedic Surgery, Tianjin Hongqiao Hospital, Tianjin, P.R. China

2Department of Immunology, Tianjin Cancer Institute and Hospital, Tianjin Medical University, P.R. China

3National Clinical Research Center of Cancer, P.R. China

4Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, P.R. China

5Immunology 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.


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