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Meis1 disrupts the genomic imprint of Dlk1 in a NUP98-HOXD13 leukemia model

Leukemia volume 24, pages 1788–1791 (2010)Cite this article

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Genomic imprinting is an epigenetic phenomenon that ensures the parental-specific expression of a subset of genes and is required for the normal mammalian development. Loss of genomic imprinting represents one of the most common genetic abnormalities in growth disorders and cancer. DNA methylation is a key component of genomic imprinting regulation in eutherian mammals, and most imprinted genes are associated with differentially methylated CpG-rich regions.

Delta-like homolog 1 (Dlk1) is an exclusively paternally expressed gene that encodes an epidermal growth factor-like transmembrane protein with homology to members of the Notch/Delta/Serrate family. Knockout mice, which are deficient in Dlk1, exhibit perturbations in megakaryocyte and B cell development.1 The role of Dlk1 in leukemogenesis is unclear as enforced overexpression of Dlk1 elicits opposing effects on proliferation in a cell-context-dependent manner.1, 2 Nevertheless, the importance of DLK1 is underscored by its frequent overexpression in myelodysplastic syndrome and acute myeloid leukemia (AML) patient samples.1 More recently, Khoury et al.3 have demonstrated that a high proportion of AML samples overexpressing DLK1 exhibited biallelic expression of DLK1 with concomitant DNA hypermethylation of associated CpG-rich regions within the imprinting control regions.

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Acknowledgements

This study was supported by the Terry Fox Foundation, Genome Canada/BC, the Cancer Research Society of Canada, the Canadian Stem Cell Network and the Leukemia Research Fund of Canada.

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Authors and Affiliations

  1. Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada

    B Argiropoulos, S Imren, M Miller, A Rouhi, D L Mager & R K Humphries

  2. Institute of Biomedicine, Sahlgrenska University Hospital, Göteborg, Sweden

    L Palmqvist

  3. Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada

    D L Mager & R K Humphries

  4. Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada

    R K Humphries

Authors
  1. B Argiropoulos
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  2. L Palmqvist
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  3. S Imren
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  4. M Miller
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  5. A Rouhi
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  6. D L Mager
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  7. R K Humphries
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Correspondence to R K Humphries.

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Argiropoulos, B., Palmqvist, L., Imren, S. et al. Meis1 disrupts the genomic imprint of Dlk1 in a NUP98-HOXD13 leukemia model. Leukemia 24, 1788–1791 (2010). https://doi.org/10.1038/leu.2010.161

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