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Myelodysplasias

Identification of disease- and therapy-associated proteome changes in the sera of patients with myelodysplastic syndromes and del(5q)

Leukemia volume 24, pages 1875–1884 (2010)Cite this article

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Abstract

Using ProteinChip array technology, which is based on the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, we performed proteomic analyses on sera from myelodysplastic syndromes (MDSs) patients with an interstitial deletion of the long arm of chromosome 5 (del(5q)) and those from control individuals. One analysis with 80 samples from 29 patients and 51 control subjects resulted in the detection of 61 peak differences. Another analysis with 36 paired-samples from 18 patients collected before and after the treatment with lenalidomide (Revlimid) identified 19 differential peak features. We also observed differential profiles between the pre-treatment samples from the responders and those from the non-responders reflected by eight peak differences. On the basis of these data we developed two classification models that could distinguish between the diseased and the control subjects or between the responders and the non-responders. Efforts were made to purify and identify a range of differential peak proteins. We conclude that inter-α trypsin inhibitor, heavy chain H4 (fragments), serum transferrin, transthyretin (variants), haemoglobin and a protein peak at m/z 2791 could be potential disease-associated markers for del(5q) MDS. Platelet factor 4 (PF-4) and a peak at m/z 8559 may serve as therapy-associated markers and be potentially useful for monitoring and predicting the response to therapy.

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Acknowledgements

This work was supported by the Leukaemia Research Fund (UK) (Grant No. LRF 07003) and the paper is submitted and published with the approval of Celegene. We thank Mr Mike Groves for preparing serum samples, Dr Fiona Paulin and Mr Douglas Lamont for proteomics services and Dr Surjeet Adlakha, Ann Hyslop, Norene Keenan and the Tayside Cancer Tissue Bank for the support in this project.

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Authors and Affiliations

  1. Division of Medical Sciences, Centre for Oncology and Molecular Medicine, College of Medicine, Dentistry & Nursing, Ninewells Hospital & Medical School, University of Dundee, Dundee, Scotland, UK

    C Chen & E G Wright

  2. Department of Haematology, St. James's Institute of Oncology, Bexley Wing, Leeds, UK

    D T Bowen

  3. Clinical Research Unit, St. Johannes Hospital, Medizinische Klinik II, Duisburg, Germany

    A A N Giagounidis & S Haase

  4. Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany

    B Schlegelberger

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  1. C Chen
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Correspondence to C Chen.

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Chen, C., Bowen, D., Giagounidis, A. et al. Identification of disease- and therapy-associated proteome changes in the sera of patients with myelodysplastic syndromes and del(5q). Leukemia 24, 1875–1884 (2010). https://doi.org/10.1038/leu.2010.182

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