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Objectiv. To investigate the contribution of TERT rs2736100 and rs2853669 gene polymorphisms in defining the genetic predisposition to 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 assays FLT3 (ITD, D835), DNMT3A (R882) and NPM1 c.863_864insTCTG (type A) mutation status was analyzed 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, FTLT3, DNM3A or NMP1 mutation, AML subtype and treatment, the estimated adjusted hasard 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 TERT rs2853669 variant genotype had a negative effect on AML patients overall survival in the presence of other known prognostic factors.

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