<p>Variability within the human <em>TERT</em> gene, telomere length and predisposition to chronic lymphocytic leukemia</p>

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.

TERT—Regulation and Roles in Cancer Formation

“…Our previous work showed that the S variant was more frequent in non-Hodgkin’s B-cell lymphoma patients how did not respond to treatment, as well as those with intermediate/high International Prognostic Index ( 159 ). In contrast, the S variant was less frequent in chronic lymphocytic leukemia patients with high disease stage ( 160 ).…”

Telomere Dysfunction in Chronic Lymphocytic Leukemia

“…Genome wide association studies repeatedly identified TERT as one among the susceptibility loci for risk of CLL ( 66 , 67 ). Studies to identify SNPs in TERT and TERC associated with CLL identified the minor rs35033501 TERT variant ( 68 ), as well as the SNPs rs10936599 in TERC and rs2736100 in TERT ( 69 ) and presence of longer telomere length to be associated with CLL. Though shortening of telomere length in CLL is well characterized to be an adverse prognostic factor it should therefore be noted that telomerase activation and telomere lengthening constitute an important phase in malignant transformation.…”

Short Dysfunctional Telomere is Highly Predictive of Dismal Outcome in MDS but Not in AML Patients

“…Cumulative knowledge from previous studies had hyopthesisd that altered telomere homeostasis plays a possible role in bone marrow failures, leukemias and other malignancies 17 . Telomere erosion in tumor cells was found to predict worse prognosis with more advanced disease in chronic lymphocytic leukemia 18,19 , myeloma 20 and various cancers 20 . Mendelian short telomere is sufficient to promote premature age-related clonal hematopoiesis, primarily associated with MDS and AML 21 .…”