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Acquired isodisomy on chromosome 13 at diagnosis results in impaired overall survival in patients with FLT3-ITD mutant acute myeloid leukaemia

Leukemia volume 29, pages 2404–2407 (2015)Cite this article

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Internal tandem duplication (ITD) mutations in the FLT3 gene on chromosome 13 occur in 25% of patients with acute myeloid leukaemia (AML) and result in impaired overall survival (OS).1 Patients with a high allelic ratio (AR) of ITD mutant to wild-type FLT3 in genomic DNA have an even poorer prognosis.2 AR may be a predictor of response to FLT3 inhibitors3 and may also interact with other mutations in influencing disease risk.4, 5

AR may be dependent on a number of factors including loss of the wild-type allele. Acquired isodisomy (AID) results in loss of the wild-type allele, through duplication of the mutant allele with segmental loss of the wild-type allele. Although studies6 have shown the importance of AID at chromosome 13 (AID13) at relapse, the impact of AID13 at diagnosis is unclear. This study aimed to identify the relationship between AID13 and FLT3-ITD AR and investigated the outcomes of patients with AID13.

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Acknowledgements

We acknowledge Christina Yap (University of Birmingham CRCTU), the scientists in the West Midlands Regional Genetics Laboratory, and the haematologists of the West Midlands.

Author contributions

JL, SA and JB collected and analysed data. JE, SWB, DC, JA, PH, JW, KA, YM, FAW, AW, AB, PF, CC and MG provided data. KB, MG and MR analysed data. JL, SA, JB and MR wrote the manuscript.

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Authors and Affiliations

  1. Centre for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, UK

    J C T Loke, J Arrazi, P Hazlewood, P Ferguson, C Craddock & M Raghavan

  2. West Midlands Regional Genetics Laboratory, Birmingham, UK

    S Akiki, J Borrow & M Griffiths

  3. Department of Haematology, Heartlands Hospital, Birmingham, UK

    J Ewing

  4. Department of Haematology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK

    S W Bokhari

  5. Department of Haematology, University Hospital of North Staffordshire, Stoke-on-Trent, UK

    D Chandra

  6. Department of Haematology, Worcestershire Royal Hospital, Worcester, UK

    K Arthur

  7. Department of Haematology, New Cross Hospital, Wolverhampton, UK

    J Walsh

  8. Department of Haematology, Sandwell and West Birmingham Hospitals NHS Trust, West Bromwich, UK

    Y Membwange & F A Wandroo

  9. Department of Haematology, Russells Hall Hospital, Dudley, UK

    A Watts

  10. Department of Haematology, South Warwickshire NHS Foundation Trust, Warwick, UK

    A Borg

  11. Cancer Research UK Clinical Trials Unit (CRCTU), University of Birmingham, Edgbaston, Birmingham, UK

    K Brock

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  1. J C T Loke
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  15. K Brock
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  16. P Ferguson
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  17. C Craddock
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  18. M Griffiths
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  19. M Raghavan
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Corresponding author

Correspondence to M Raghavan.

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The authors declare no conflict of interest.

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Supplementary Information accompanies this paper on the Leukemia website

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Loke, J., Akiki, S., Borrow, J. et al. Acquired isodisomy on chromosome 13 at diagnosis results in impaired overall survival in patients with FLT3-ITD mutant acute myeloid leukaemia. Leukemia 29, 2404–2407 (2015). https://doi.org/10.1038/leu.2015.148

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