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Differentially expressed genes in adult familial myelodysplastic syndromes

Leukemia volume 18, pages 449–459 (2004)Cite this article

Abstract

The precise genetic events leading to myelodysplastic syndromes (MDSs) and leukemic transformation remain poorly defined. Even less is known about adult familial MDS. We report an adult MDS family in whom enriched tissue-specific transcripts were derived by subtractive hybridization of cDNA from the mononuclear and CD34+ cells of affected and unaffected family members. These expression libraries were then hybridized to Genome Discovery arrays containing 18 404 genes and expressed sequence tags, and several clusters of differentially expressed genes were identified. A group of 21 genes was underexpressed (>5-fold) in affected vs unaffected family members, and among these were transcription factors and genes involved in myeloid differentiation, such as ZNF140 and myeloid nuclear differentiation antigen (MNDA). Another group of 36 genes was overexpressed (>5-fold), and these encoded proteins belonging to signaling pathways, such as Ras- and Fos-related genes. The top two genes downregulated in this MDS family, ZNF140 and MNDA, were similarly altered in another MDS family, and in some cases of sporadic MDS. Our data suggest that we have identified genes differentially expressed in adult familial MDS, and that alteration of some of these genes may also be important for the evolution of different stages or severity of sporadic MDS.

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Acknowledgements

We thank Dr Tohayama, Kyoto University (Japan), for providing the MDS92L cell line and Dr Don Milligan, Birmingham Heartlands Hospital (UK), for supplying material and data on MDS family 2. We also thank Drs Shaun Thomas, Barbara Guinn and Rose Ann Padua (GKT School of Medicine, UK), and Professor Stephen Baylin (Johns Hopkins School of Medicine, Baltimore, USA) for critical reading of our manuscript. This study was supported by the Joint Research Council (JRC) of King's College London. AP was supported by JRC studentship 229 and FVR was supported by the Elimination of Leukemia Fund.

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Authors and Affiliations

  1. Department of Haematological Medicine, Leukaemia Science Laboratories, The Rayne Institute, GKT School of Medicine, Denmark Hill, London, UK

    A Pradhan, A Mijovic, N Westwood, G J Mufti & F V Rassool

  2. Department of Haematology, University of Wales College of Medicine, Cardiff, UK

    K Mills

  3. West Wales General Hospital, Carmarthen, UK

    P Cumber

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  1. A Pradhan
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Correspondence to F V Rassool.

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Pradhan, A., Mijovic, A., Mills, K. et al. Differentially expressed genes in adult familial myelodysplastic syndromes. Leukemia 18, 449–459 (2004). https://doi.org/10.1038/sj.leu.2403265

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