Variability within the human TERT gene, telomere length and predisposition to chronic lymphocytic leukemia

Barbara Wysoczanska; Marta Dratwa; Katarzyna Gebura; Jakub Mizgala; Grzegorz Mazur; Tomasz Wrobel; Katarzyna Bogunia-Kubik

doi:10.2147/OTT.S198313

Variability within the human TERT gene, telomere length and predisposition to chronic lymphocytic leukemia

Onco Targets Ther. 2019 May 31:12:4309-4320. doi: 10.2147/OTT.S198313. eCollection 2019.

Authors

Barbara Wysoczanska¹, Marta Dratwa¹, Katarzyna Gebura¹, Jakub Mizgala¹, Grzegorz Mazur², Tomasz Wrobel³, Katarzyna Bogunia-Kubik¹

Affiliations

¹ Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw 53-114, Poland.
² Department of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, Wroclaw, 50-001, Poland.
³ Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw 50-367, Poland.

Abstract

Background: The human telomerase reverse transcriptase (TERT) gene encodes the catalytic subunit of telomerase that is essential for maintenance of telomere length. We aimed to find out whether variability within the TERT gene could be associated with telomere length and development of the disease in non-treated patients with chronic lymphocytic leukemia (CLL). Materials and methods: Telomere length, rs2736100, rs2853690, rs33954691, rs35033501 single-nucleotide polymorphisms, and variable number of tandem repeats (VNTR-MNS16A) were assessed in patients at diagnosis. In addition, blood donors served as controls for the polymorphism studies. Results: The minor rs35033501 A variant was more frequent among CLL patients than in healthy controls (OR=3.488, p=0.039). CLL patients over 60 years of age were characterized with lower disease stage at diagnosis (p=0.001 and p=0.008, for the Rai and Binet criteria, respectively). The MNS16A VNTR-243 short allele was more frequent in patients with a low disease stage (p=0.020 and p=0.028, for the Rai and Binet staging system) and also among older patients having longer telomeres (p=0.046). Patients with Rai 0-I stage were characterized with longer telomeres than those with more advanced disease (p=0.030). This relationship was especially pronounced in patients carrying the rs2736100 C allele, independently of the criteria used, ie, Binet (p=0.048) or Rai (p=0.001). Conclusion: Our results showed that the genetic variation within the TERT gene seems to play a regulatory role in CLL and telomere length.

Keywords: chronic lymphocytic leukemia; human telomerase reverse transcriptase; single-nucleotide polymorphism; telomere length; variable number of tandem repeats.