Institute of Experimental Cancer Research, Comprehensive Cancer Center and University Hospital Ulm, Albert-Einstein-Allee 11, Ulm, Germany.
Exp Hematol. 2011 Mar;39(3):272-81. doi: 10.1016/j.exphem.2010.12.004. Epub 2010 Dec 17.
Stem cells are defined as cells that have the ability to perpetuate themselves through self-renewal and to generate functional mature cells by differentiation. During each stage, coordinated gene expression is crucial to maintain the balance between self-renewal and differentiation. Disturbance of this accurately balanced system can lead to a variety of malignant disorders. In mammals, DNA cytosine-5 methylation is a well-studied epigenetic pathway that is catalyzed by DNA methyltransferases and is implicated in the control of balanced gene expression, but also in hematological malignancies. In this review, we focus on the TET (ten-eleven-translocation) genes, which recently were identified to catalyze the conversion of cytosine-5 methylation to 5-hydroxymethyl-cytosine, an intermediate form potentially involved in demethylation. In addition, members of the TET family are playing a role in ES cell maintenance and inner cell mass cell specification and were demonstrated to be involved in hematological malignancies. Recently, a correlation between low genomic 5-hydroxymethyl-cytosine and TET2 mutation status was shown in patients with myeloid malignancies.
干细胞被定义为具有自我更新能力的细胞，可以通过分化产生功能性成熟细胞。在每个阶段，协调的基因表达对于维持自我更新和分化之间的平衡至关重要。这个精确平衡系统的紊乱可能导致各种恶性疾病。在哺乳动物中，DNA 胞嘧啶-5 甲基化是一种经过充分研究的表观遗传途径，它由 DNA 甲基转移酶催化，与平衡基因表达的控制有关，但也与血液恶性肿瘤有关。在这篇综述中，我们重点介绍了 TET（十-十一易位）基因，这些基因最近被鉴定为催化胞嘧啶-5 甲基化转化为 5-羟甲基胞嘧啶，这是一种潜在参与去甲基化的中间形式。此外，TET 家族的成员在胚胎干细胞维持和内细胞团细胞特化中发挥作用，并被证明与血液恶性肿瘤有关。最近，在患有骨髓恶性肿瘤的患者中显示出基因组低 5-羟甲基胞嘧啶与 TET2 突变状态之间存在相关性。
