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Whole-exome sequencing in del(5q) myelodysplastic syndromes in transformation to acute myeloid leukemia

Leukemia volume 28, pages 1148–1151 (2014)Cite this article

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Myelodysplastic syndromes (MDSs) are clonal disorders of the hematopoietic stem cell.1 MDS represents an excellent model of leukemic transformation with ∼30–40% of MDS patients developing acute myeloid leukemia (AML).1 The molecular basis of leukemic transformation in MDS remains poorly understood and there is a compelling need to identify the specific molecular events driving this process. Recently, whole-exome sequencing (WES) has been used to identify novel gene mutations in myeloid malignancies, including MDS.2 The value of this approach in the study of MDS transforming to AML has recently been illustrated by Walter et al.3 To date, however, only a small number of cases of MDS have been thus studied.

Interstitial deletion within the long arm of chromosome 5 (del(5q)) is one of the most frequent cytogenetic abnormalities observed in MDS, occurring in ∼10–20% of patients.4 In order to investigate the molecular events associated with disease progression in MDS with del(5q), we performed WES on paired samples from two MDS cases with del(5q) (patient 1 and patient 2) and one MDS case without del(5q) (patient 3) before and after progression to AML. Genomic DNA was isolated from bone marrow cells collected at the time of diagnosis and at leukemic transformation (following informed consent) and subjected to WES. T cells were used as a source of constitutional DNA (CD3+ cells, purity >97%). Tumor and constitutional DNA were used for exome capture and high-throughput sequence analysis using Illumina technology (San Diego, CA, USA).

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Acknowledgements

This work was supported by Leukaemia and Lymphoma Research of the United Kingdom and by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Programme. Whole-exome sequencing was performed at the Oxford Genomics Centre, Wellcome Trust Centre for Human Genetics, Oxford, UK.

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The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.

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Author notes

  1. A Pellagatti, M Fernandez-Mercado and C Di Genua: These authors contributed equally to this work.

Authors and Affiliations

  1. Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, LLR Molecular Haematology Unit, University of Oxford, Oxford, UK

    A Pellagatti, M Fernandez-Mercado, C Di Genua, H Dolatshad & J Boultwood

  2. Department of Genetics, University of Navarra, Pamplona, Spain

    M J Larrayoz & M J Calasanz

  3. Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK

    S Killick

  4. NIHR Biomedical Research Centre, University of Oxford,

    A Burns & A Schuh

  5. Oxford, UK

    A Burns & A Schuh

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  1. A Pellagatti
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  2. M Fernandez-Mercado
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  3. C Di Genua
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Corresponding author

Correspondence to J Boultwood.

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Pellagatti, A., Fernandez-Mercado, M., Di Genua, C. et al. Whole-exome sequencing in del(5q) myelodysplastic syndromes in transformation to acute myeloid leukemia. Leukemia 28, 1148–1151 (2014). https://doi.org/10.1038/leu.2013.381

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