Identifying the biomarker potential of telomerase activity and shelterin complex molecule, telomeric repeat binding factor 2 (TERF2), in multiple myeloma

Abstract

Telomere length (TL) is maintained by telomere capping protein complex called shelterin complex. We studied the possible involvement and biomarker potential of shelterin complex molecules in naive multiple myeloma (MM) patients and controls. TL, relative telomerase activity (RTA), real-time PCR and Western blotting were performed in bonemarrow sample of 70 study subjects (patients = 50; controls = 20). Significantly lowered mean TL, increased RTA and higher mRNA expression of shelterin molecules were observed in patients, while PIN2/TERF1 interacting telomerase inhibitor 1 (PINX1) showed lower mRNA expression. Significantly increased protein expression of telomeric repeat binding factor 2 (TERF2), protection of telomeres 1, adrenocortical dysplasia homolog, Tankyrase 1 and telomere reverse transcriptase were observed in MM patients. Significant correlation was observed among genes and of genes with clinical parameters. In conclusion, our findings showed alteration of these molecules at mRNA and protein levels suggested their involvement in disease progression. Optimal sensitivity and specificity of TERF2 and RTA on receiver operating characteristics curve analysis and univariate analysis demonstrated their biomarkers potential in better prediction of disease course.

Keywords:

• Myeloma
• shelterin complex
• TERF2
• telomerase activity
• biomarker
• prognostication

Acknowledgements

Financial assistance to Mr. Raman Kumar as Senior Research Fellow by Indian Council of Medical Research, New Delhi, India, is acknowledged.

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article online at https://doi.org/10.1080/10428194.2017.1387915.