Division of Hematology, Kitasato University School of Allied Health Sciences; Division of Molecular Hematology, Kitasato University Graduate School of Medical Sciences, Sagamihara, Kanagawa 252-0373, Japan.
Int J Mol Med. 2013 Sep;32(3):532-8. doi: 10.3892/ijmm.2013.1417. Epub 2013 Jun 12.
The development of novel technologies, such as massively parallel DNA sequencing, has led to the identification of several novel recurrent gene mutations, such as DNA methyltransferase (Dnmt)3a, ten-eleven-translocation oncogene family member 2 (TET2), isocitrate dehydrogenase (IDH)1/2, additional sex comb-like 1 (ASXL1), enhancer of zeste homolog 2 (EZH2) and ubiquitously transcribed tetratricopeptide repeat X chromosome (UTX) mutations in acute myeloid leukemia (AML) and other myeloid malignancies. These findings strongly suggest a link between recurrent genetic alterations and aberrant epigenetic regulations, resulting from an abnormal DNA methylation and histone modification status. This review focuses on the current findings of aberrant epigenetic signatures by these newly described genetic alterations. Moreover, epigenetic aberrations resulting from transcription factor aberrations, such as mixed lineage leukemia (MLL) rearrangement, ecotropic viral integration site 1 (Evi1) overexpression, chromosomal translocations and the downregulation of PU.1 are also described.
新的技术如大规模平行 DNA 测序的发展，已确定了几种新的基因频发突变，如 DNA 甲基转移酶（Dnmt）3a、十号染色体缺失与张力蛋白同源的基因 2（TET2）、异柠檬酸脱氢酶（IDH）1/2、额外的性梳样蛋白 1（ASXL1）、增强子 of zeste 同源物 2（EZH2）和广泛转录四肽重复 X 染色体（UTX）突变在急性髓细胞白血病（AML）和其他髓系恶性肿瘤中。这些发现强烈提示频发遗传改变与异常表观遗传调控之间存在关联，这种异常主要源于异常的 DNA 甲基化和组蛋白修饰状态。这篇综述主要关注这些新描述的遗传改变所导致的异常表观遗传特征的最新发现。此外，转录因子异常如混合谱系白血病（MLL）重排、ectopic viral integration site 1（Evi1）过表达、染色体易位和 PU.1 下调也会导致表观遗传异常。
