1. ¹Department of Cellular Biotechnologies and Hematology, 'La Sapienza' University of Rome, Rome, Italy
2. ²San Raffaele Bio-medical Park Foundation, Rome, Italy
3. ³Department of Histology and Medical Embryology, 'La Sapienza' University of Rome, Rome, Italy

Correspondence: Professor C Nervi, Department of Histology and Medical Embryology, 'La Sapienza' University of Rome, Rome, Italy and San Raffaele Bio-medical Park Foundation, Via di Castel Romano 100, Rome 00128, Italy. E-mail: clara.nervi@uniroma1.it

Received 12 October 2007; Revised 24 April 2008; Accepted 5 May 2008; Published online 12 June 2008.

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.