Association between TERT promoter polymorphisms and acute myeloid leukemia risk and prognosis

// Mohamed Ali Mosrati 1 , Kerstin Willander 2 , Ingrid Jakobsen Falk 3 , Monica Hermanson 4 , Martin Hoglund 5 , Dick Stockelberg 6 , Yuan Wei 6 , Kourosh Lotfi 3, 7 , Peter Soderkvist 1 1 Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden 2 Department of Haematology and Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden 3 Department of Medical and Health Sciences, Linkoping University, Linkoping, Sweden 4 Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden 5 Division of Hematology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden 6 Section for Hematology and Coagulation, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden 7 Department of Hematology, County Council of Ostergotland, Linkoping, Sweden Correspondence to: Mohamed Ali Mosrati, e-mail: mohamed.ali.mosrati@liu.se Keywords: TERT, SNV, AML, prognostic markers Received: May 11, 2015      Accepted: July 10, 2015      Published: July 23, 2015 ABSTRACT Telomerase reverse transcriptase gene ( TERT ) promoter mutations are identified in many malignancies but not in hematological malignancies. Here we analyzed TERT and protection of telomeres 1 gene ( POT1) mutations, and four different TERT SNVs in 226 acute myeloid leukemia (AML) patients and 806 healthy individuals in a case referent design, where also overall survival was assessed. A significant association for increased risk of AML was found for TERT SNVs, rs2853669 (OR = 2.45, p = 0.00015) and rs2736100 (OR = 1.5, p = 0.03). The overall survival for patients with CC genotype of rs2853669 was significantly shorter compared to those with TT or TC genotypes ( p = 0.036 and 0.029 respectively). The influence of TERT rs2853669 CC on survival was confirmed in multivariable Cox regression analysis as an independent risk biomarker in addition to high risk group, higher age and treatment. No hot spot TERT promoter mutations at −228C > T or −250C > T or POT1 mutations could be identified in this AML cohort. We show that rs2853669 CC may be a risk factor for the development of AML that may also be used as a prognostic marker to identify high risk normal karyotype-AML (NK-AML) patients, for treatment guidance.