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

Jenna Williams, Nicole H. Heppel, Bethan Britt-Compton, Julia W. Grimstead, Rhiannon E. Jones, Sudhir Tauro, David T. Bowen, Steven Knapper, Michael Groves, Robert K. Hills, Chris Pepper, Duncan M. Baird, Chris Fegan (Lead / Corresponding author)

Research output: Contribution to journalArticle

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Abstract

Telomere dysfunction is implicated in the generation of large-scale genomic rearrangements which drives progression to malignancy. In this study we used high-resolution single telomere length analysis (STELA) to examine the potential role of telomere dysfunction in 80 Myelodysplasia (MDS) and 95 de novo Acute Myeloid Leukaemia (AML) patients. Despite the MDS cohort being older they had significantly longer telomeres than the AML cohort (P<.0001) where telomere length was also significantly shorter in younger AML patients (age <60) (P = .02) and in FLT3 ITD mutated AML patients (P = .03). Using a previously determined telomere length threshold for telomere dysfunction (3.81kb) did not provide prognostic resolution in AML (HR = 0.68, P = .2). In contrast, the same length threshold was highly prognostic for overall survival in the MDS cohort (HR = 5.0, P <.0001). Furthermore, this telomere length threshold was an independent parameter in multivariate analysis when adjusted for age, gender, cytogenetic risk group, number of cytopenias and IPSS score (HR = 2.27, P < .0001). Therefore, telomere length should be assessed in a larger prospective study to confirm its prognostic role in MDS with a view to integrating this variable into a revised IPSS.
Original languageEnglish
Pages (from-to)240-249
Number of pages10
JournalBritish Journal of Haematology
Volume178
Issue number2
Early online date9 May 2017
DOIs
Publication statusPublished - 11 Jul 2017

Keywords

  • Myelodysplasia
  • AML
  • Telomere
  • Telomerase

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