Telomere length is an independent prognostic marker in MDS but not in de novo AML

Williams, Jenna, Heppel, Nicole H, Britt-Compton, Bethan, Grimstead, Julia W, Jones, Rhiannon E, Tauro, Sudhir, Bowen, David T, Knapper, Steven, Groves, Michael, Hills, Robert K, Pepper, Chris, Baird, Duncan M and Fegan, Chris (2017) Telomere length is an independent prognostic marker in MDS but not in de novo AML. British Journal of Haematology, 178 (2). pp. 240-249. ISSN 0007-1048

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Telomere dysfunction is implicated in the generation of large-scale genomicrearrangements that drive progression to malignancy. In this study we usedhigh-resolution single telomere length analysis (STELA) to examine thepotential role of telomere dysfunction in 80 myelodysplastic syndrome(MDS) and 95de novoacute myeloid leukaemia (AML) patients. Despitethe MDS cohort being older, they had significantly longer telomeres thanthe AML cohort (P<0.0001) where telomere length was also significantlyshorter in younger AML patients (age<60 years) (P=0.02) and inFLT3internal tandem duplication-mutated AML patients (P=0.03). Using apreviously determined telomere length threshold for telomere dysfunction(3.81 kb) did not provide prognostic resolution in AML [Hazard ratio(HR)=0.68,P=0.2]. In contrast, the same length threshold was highlyprognostic for overall survival in the MDS cohort (HR=5.0,P<0.0001).Furthermore, this telomere length threshold was an independent parameterin multivariate analysis when adjusted for age, gender, cytogenetic riskgroup, number of cytopenias and International Prognostic Scoring System(IPSS) score (HR=2.27,P<0.0001). Therefore, telomere length shouldbe assessed in a larger prospective study to confirm its prognostic role inMDS with a view to integrating this variable into a revised IPSS.

Item Type: Article
Keywords: AML ; myelodysplasia; telomerase; telomere
Schools and Departments: Brighton and Sussex Medical School > Clinical and Experimental Medicine
Depositing User: Gemma Hamilton
Date Deposited: 07 Feb 2018 15:10
Last Modified: 26 Feb 2018 16:25

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