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

Mohamed Ali Mosrati; Kerstin Willander; Ingrid Jakobsen Falk; Monica Hermanson; Martin Höglund; Dick Stockelberg; Yuan Wei; Kourosh Lotfi; Peter Söderkvist

doi:10.18632/oncotarget.4668

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Research Papers:

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

Mohamed Ali Mosrati _, Kerstin Willander, Ingrid Jakobsen Falk, Monica Hermanson, Martin Höglund, Dick Stockelberg, Yuan Wei, Kourosh Lotfi and Peter Söderkvist

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Oncotarget. 2015; 6:25109-25120. https://doi.org/10.18632/oncotarget.4668

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Abstract

Mohamed Ali Mosrati1, Kerstin Willander2, Ingrid Jakobsen Falk3, Monica Hermanson4, Martin Höglund5, Dick Stockelberg6, Yuan Wei6, Kourosh Lotfi3,7, Peter Söderkvist1

1Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden

2Department of Haematology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden

3Department of Medical and Health Sciences, Linköping University, Linköping, Sweden

4Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden

5Division of Hematology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden

6Section for Hematology and Coagulation, Department of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden

7Department of Hematology, County Council of Östergötland, Linköping, Sweden

Correspondence to:

Mohamed Ali Mosrati, e-mail: [email protected]

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.

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Research Papers:

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

Abstract