TERT rs2853669 as a predictor for overall survival in patients with acute myeloid leukaemia

Florin Tripon; Claudia Bănescu; Adrian P Trifa; Andrei G Crauciuc; Valeriu G Moldovan; Alina Boglis; Istvan Benedek; Smaranda Demian; Carmen Duicu; Mihaela Iancu

doi:10.5114/aoms/100673

TERT rs2853669 as a predictor for overall survival in patients with acute myeloid leukaemia

Arch Med Sci. 2021 Mar 18;18(1):103-111. doi: 10.5114/aoms/100673. eCollection 2022.

Authors

Affiliations

¹ Department of Medical Genetics, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Romania.
² Genetics Laboratory, Centre for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Romania.
³ Department of Medical Genetics, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
⁴ Department of Internal Medicine, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Romania.
⁵ Department of Clinical Science, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Romania.
⁶ Department of Medical Informatics and Biostatistics, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.

Abstract

Introduction: the aim of the study was to investigate the contribution of TERT rs2736100 and rs2853669 gene polymorphisms in defining the genetic predisposition to acute myeloid leukaemia (AML), their association with different prognostic markers, and their impact on survival, outcome, and the prognosis of affected patients. Also, we investigated the association of TERT SNPs in AML in the presence or absence of DNMT3A (R882), NPM1, and FLT3 mutations.

Material and methods: A total of 509 participants were enrolled in our study, consisting of 146 AML patients and 363 healthy participants, with no history of malignancy. TERT rs2736100 and rs2853669 polymorphisms were genotyped by using TaqMan SNP genotyping assay FLT3 (ITD, D835), DNMT3A (R882), and NPM1 c.863_864insTCTG (type A) mutations were analised in each AML case.

Results: TERT rs2736100 and rs2853669 were not associated with AML risk in the codominant, dominant, recessive, or allelic models. Multivariate Cox regression showed that TERT rs2853669 was a significant predictor for overall survival in AML patients. After adjusting for age, gender, cytogenetic risk group, ECOG status, FLT3, DNMT3A, NPM1 mutation, AML subtype, and treatment, the estimated adjusted hazard ratio (HR adjusted = 1.54, 95% CI: 1.01-2.35) showed that the TERT rs2853669 variant genotype had a negative influence on survival time.

Conclusions: TERT rs2853669 and rs2736100 polymorphisms were not risk factors for developing AML in the Romanian population, but the TERT rs2853669 variant genotype had a negative effect on AML patients' overall survival in the presence of other known prognostic factors.

Keywords: TERT gene polymorphism; acute myeloid leukaemia; overall survival; predictor.