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

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Telomere
Acute Myeloid Leukemia
Cytogenetics
Multivariate Analysis
Prospective Studies
Survival

Keywords

  • Myelodysplasia
  • AML
  • Telomere
  • Telomerase

Cite this

Williams, J., Heppel, N. H., Britt-Compton, B., Grimstead, J. W., Jones, R. E., Tauro, S., ... Fegan, C. (2017). Telomere length is an independent prognostic marker in MDS but not in de novo AML. British Journal of Haematology, 178(2), 240-249. https://doi.org/10.1111/bjh.14666
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. ; Fegan, Chris. / Telomere length is an independent prognostic marker in MDS but not in de novo AML. In: British Journal of Haematology. 2017 ; Vol. 178, No. 2. pp. 240-249.
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title = "Telomere length is an independent prognostic marker in MDS but not in de novo AML",
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.",
keywords = "Myelodysplasia, AML , Telomere, Telomerase",
author = "Jenna Williams and Heppel, {Nicole H.} and Bethan Britt-Compton and Grimstead, {Julia W.} and Jones, {Rhiannon E.} and Sudhir Tauro and Bowen, {David T.} and Steven Knapper and Michael Groves and Hills, {Robert K.} and Chris Pepper and Baird, {Duncan M.} and Chris Fegan",
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Williams, J, Heppel, NH, Britt-Compton, B, Grimstead, JW, Jones, RE, Tauro, S, Bowen, DT, Knapper, S, Groves, M, Hills, RK, Pepper, C, Baird, DM & Fegan, C 2017, 'Telomere length is an independent prognostic marker in MDS but not in de novo AML', British Journal of Haematology, vol. 178, no. 2, pp. 240-249. https://doi.org/10.1111/bjh.14666

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.; Fegan, Chris (Lead / Corresponding author).

In: British Journal of Haematology, Vol. 178, No. 2, 11.07.2017, p. 240-249.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Telomere length is an independent prognostic marker in MDS but not in de novo AML

AU - Williams, Jenna

AU - Heppel, Nicole H.

AU - Britt-Compton, Bethan

AU - Grimstead, Julia W.

AU - Jones, Rhiannon E.

AU - Tauro, Sudhir

AU - Bowen, David T.

AU - Knapper, Steven

AU - Groves, Michael

AU - Hills, Robert K.

AU - Pepper, Chris

AU - Baird, Duncan M.

AU - Fegan, Chris

N1 - This work was funded by Cancer Research UK and Bloodwise grants 12049 and 13033.

PY - 2017/7/11

Y1 - 2017/7/11

N2 - 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.

AB - 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.

KW - Myelodysplasia

KW - AML

KW - Telomere

KW - Telomerase

U2 - 10.1111/bjh.14666

DO - 10.1111/bjh.14666

M3 - Article

C2 - 28486748

VL - 178

SP - 240

EP - 249

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 2

ER -

Williams J, Heppel NH, Britt-Compton B, Grimstead JW, Jones RE, Tauro S et al. Telomere length is an independent prognostic marker in MDS but not in de novo AML. British Journal of Haematology. 2017 Jul 11;178(2):240-249. https://doi.org/10.1111/bjh.14666