Zardo G, Cimino G, Nervi C
Department of Cellular Biotechnologies and Hematology, La Sapienza University of Rome, Rome, Italy.
Leukemia. 2008 Aug;22(8):1503-18. doi: 10.1038/leu.2008.141. Epub 2008 Jun 12.
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.
在胚胎发育和成年期,影响染色质结构的修饰的可塑性和可逆性对于参与细胞命运决定和维持细胞分化状态的基因表达至关重要。DNA和染色质的表观遗传变化必须发生,以使转录因子能够接近特定的DNA结合位点,这些变化被认为是胚胎和造血干细胞(HSC)发育以及谱系分化的主要参与者。基因表达的表观遗传失调,无论是否与染色体改变和基因突变相关,都是一种新认识到的导致多种疾病(包括白血病)的机制。表观遗传修饰的可逆性使得DNA和染色质变化成为治疗干预的有吸引力的靶点。在这里,我们综述了一些调节多能胚胎和多能造血干细胞中基因表达但可能在白血病中失调的表观遗传机制,以及旨在靶向白血病细胞中染色质结构的临床方法。