title: MDS shows a higher expression of hTERT and alternative splice variants in unactivated T-cells.
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.
authors.affiliation: Department of Orthopaedic Surgery, Tianjin Hongqiao Hospital, Tianjin, P.R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Dong
authors.affiliation: Department of Immunology, Tianjin Cancer Institute and Hospital, Tianjin Medical University, P.R. China.|National Clinical Research Center of Cancer, P.R. China.|Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Immunology, Tianjin Cancer Institute and Hospital, Tianjin Medical University, P.R. China.|National Clinical Research Center of Cancer, P.R. China.|Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, P.R. China.
authors.forename: Houfang
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Immunology, Tianjin Cancer Institute and Hospital, Tianjin Medical University, P.R. China.|National Clinical Research Center of Cancer, P.R. China.|Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, P.R. China.
authors.forename: Xiubao
authors.initials: X
authors.lastname: Ren
authors.affiliation: Immunology Program at the H. Lee Moffitt Cancer Center, Tampa, FL, USA.
authors.forename: Pearlie K
authors.initials: PK
authors.lastname: Epling-Burnette
authors.affiliation: Department of Immunology, Tianjin Cancer Institute and Hospital, Tianjin Medical University, P.R. China.|National Clinical Research Center of Cancer, P.R. China.|Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, P.R. China.
authors.forename: Lili
authors.initials: L
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000209:etiology / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000378:metabolism*; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism; D016615:Telomere
chemical_list: D012333:RNA, Messenger; C509186:TERT protein, human; D019098:Telomerase
keywords: MDS; T-cells; hTERT; hTERT alternative splice variants; telomerase