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

Leuk Lymphoma. 2018 Jul;59(7):1677-1689. doi: 10.1080/10428194.2017.1387915. Epub 2017 Oct 18.

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; TERF2; biomarker; prognostication; shelterin complex; telomerase activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor*
  • Biopsy
  • Bone Marrow / pathology
  • Case-Control Studies
  • Enzyme Activation
  • Gene Expression
  • Humans
  • Middle Aged
  • Multiple Myeloma / genetics
  • Multiple Myeloma / metabolism*
  • Multiple Myeloma / mortality
  • Multiple Myeloma / pathology
  • Neoplasm Staging
  • Prognosis
  • Telomere / genetics
  • Telomere / metabolism*
  • Telomere Homeostasis
  • Telomeric Repeat Binding Protein 2 / metabolism*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • TERF2 protein, human
  • Telomeric Repeat Binding Protein 2