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Epigenetic plasticity of chromatin in embryonic and hematopoietic stem/progenitor cells: therapeutic potential of cell reprogramming

Leukemia volume 22, pages 1503–1518 (2008)Cite this article

Abstract

During embryonic development and adult life, the plasticity and reversibility of modifications that affect the chromatin structure is important in the expression of genes involved in cell fate decisions and the maintenance of cell-differentiated state. Epigenetic changes in DNA and chromatin, which must occur to allow the accessibility of transcriptional factors at specific DNA-binding sites, are regarded as emerging major players for embryonic and hematopoietic stem cell (HSC) development and lineage differentiation. Epigenetic deregulation of gene expression, whether it be in conjunction with chromosomal alterations and gene mutations or not, is a newly recognized mechanism that leads to several diseases, including leukemia. The reversibility of epigenetic modifications makes DNA and chromatin changes attractive targets for therapeutic intervention. Here we review some of the epigenetic mechanisms that regulate gene expression in pluripotent embryonic and multipotent HSCs but may be deregulated in leukemia, and the clinical approaches designed to target the chromatin structure in leukemic cells.

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Acknowledgements

We thank all our past and current collaborators for expertize and discussions. We apologize that due to space limitations many crucial references were not directly cited but they can be found in cited reviews. This study was supported partially by grants from the Associazione Italiana per Ricerca sul Cancro (AIRC), Associazione Italiana contro le Leucemie Sezione di Roma (ROMAIL), ‘La Sapienza’ University of Rome and Italian Ministry for Universities and Research (MIUR).

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  1. Department of Cellular Biotechnologies and Hematology, ‘La Sapienza’ University of Rome, Rome, Italy

    G Zardo & G Cimino

  2. San Raffaele Bio-medical Park Foundation, Rome, Italy

    G Zardo & C Nervi

  3. Department of Histology and Medical Embryology, ‘La Sapienza’ University of Rome, Rome, Italy

    C Nervi

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  1. G Zardo
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Zardo, G., Cimino, G. & Nervi, C. Epigenetic plasticity of chromatin in embryonic and hematopoietic stem/progenitor cells: therapeutic potential of cell reprogramming. Leukemia 22, 1503–1518 (2008). https://doi.org/10.1038/leu.2008.141

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