Epigenetics refers to the independent process of inherited DNA sequences that regulate the expression of genes. Epigenetic modifications control genetic coding processes and cellular differentiation, particularly its role in mouse hematopoietic development in the dynamic regulation of specific target genes during differentiation. The researchers found that, consistent with changes in gene expression during hematopoietic differentiation, normal DNA methylation patterns also occur during differentiation of specific hematopoietic lineages. As imagined, specific hematopoietic cells require promoters of genes, which are usually derived from progenitor cell differentiation, for which genes primarily maintain a stem or progenitor cell state, such as the (MEIS1) and A9 (HOXA9) homologs, undergo increasing methylation differences. DNMT3A and DNA methylation DNMT3A is a member of a family of mammalian methylation transferase profiles that add methylcytosine to CpG dinucleotides of DNA. ley and his colleagues first identified somatic mutations in DNMT3A in adult patients with AML, and they performed whole-genome sequencing of human samples with AML that had normal cellular inheritance. They identified mutations in DNMT3A in 22% of AML patients and associated them with a risk of relapse. Another study with a sample size of 489 AML cases showed that DNMT3A mutations led to a worse prognosis and reduced overall survival. Notably, most DNMT3A mutations result in truncation of the protein product (nonsense or shift mutations) or occur at a single amino acid – R882. mutations in R882 occur in nearly 60% of DNMT3A mutations (37/62) and reduce catalytic activity and DNA affinity. TET2 and DNA hydroxymethylation TET family proteins were first identified in the TET1 clone, a clone that accompanies t(10;11)(q22;q23) in AML cases of MLL. Recent studies have shown that TET proteins (TET1C3) are Fe(II) and α?α-ketoglutarate-dependent enzymes that catalyze the change of 5-MC to 5-HMC. inactivating mutations and somatic mutations in TET2 were identified in MPN and MDS within the minimal region of chromosome 4q24 based on loss-mapping heterozygosity deletion. mutations in TET2 occur in 10-20 percent of MPN and MDS cases, and 7-23 percent of AML cases. Although the results of clinically relevant studies have not been harmonized, in the largest study, TET2 mutations were found to result in a poorer prognosis in patients with AML with good risk and normal karyotype, while studies failed to reach consistent conclusions in patients with MPN and MDS. In vitro studies have shown that shRNA-mediated silencing of TET2 expression leads to impaired hematopoietic differentiation. In recent studies, it was found that TET2 knockout mouse models also cause MDS-like symptoms, including increased erythroid progenitor cells. The phenotypic differences in these studies may be due to the different approaches to TET2 studies. Of interest, IDH1 and IDH2: IDH1 and IDH2 catalyze a very important step in the conversion of citric acid to α-ketoglutarate via the Krebs cycle via an NADP+-dependent pathway. idH1 functions in the cytoplasm and peroxidase body weight, while IDH2 is in the mitochondria. idH1 mutations were first identified in whole genome sequencing IDH1 mutations were first identified in whole genome sequencing and confirmed in 149 glioma samples in which 12% of IDH1 mutations were present. IDH1 mutations are also present in diseases such as chondrosarcoma, bile duct cancer, colorectal cancer, and thyroid cancer. Tumor-associated IDH1 and IDH2 mutations occur on three highly conserved arginine residues: IDH1?-R132, IDH2?-R172 and IDH2?-R140. serum 2-HG levels are significantly elevated in AML patients with IDH1 and IDH2 mutations, suggesting that 2-HG is a biomarker for IDH-mutant AML. In addition to the TET family, other α?ketoglutarate-dependent enzymes are similarly inhibited by 2-HG. In particular, the jumonji family of histone lysine methylesterases (JMJC), which methylates histone lysines 9 and 36, has been shown to be inhibited by 2-HG. Other α-ketoglutarate-dependent oxygenases include enzymes involved in hypoxia sensitivity, collagen biosynthesis, lipid synthesis and DNARNA methylation. tET2 mutations directly affect TET2 function, whereas 2?-ketoglutarate-dependent enzymes result from impaired IDH1 and IDH2 mutations, which could explain the spectrum and correlation of TET2 and IDH1/IDH2 mutations in myeloid malignancies differences. Mutations in histone modifying enzymes Mutations in the EZH2 gene are associated with PRC2 gene deletion in myeloid malignancies. polycomb histones (PcG) are transcriptional repressors that are essential for regulating cell differentiation and maintaining cell function in different environments. pcG requires at least two different complexes to function, PRC1 and PRC2. these complexes play an extremely important role in vertebrate development. The PcG protein complex initiates and maintains transcriptional silencing through specific post-translational histone modifications. the PRC2 complex consists of four core members: EZH1 and EZH2, embryonic ectodermal development (EED), zeste homolog 12 (SUZ12) and the RbAp48 protein (also known as RBBP4). In contrast, PRC1 is more commonly thought of as a collection of different complexes based on the replication of core PRC1 complex genes among Drosophila and mammals. The mammalian PRC1 complex is thought to be composed of two core members RING1A and RING1B with one of the following: BMI1, mel18 (also known as pcgf2) or NSPc1 protein (also known as pcgf1). The PcG member most often used to explain the pathogenesis of human malignancies is EZH2 – a component of the PRC2 complex enzyme.EZH2 is an H3K27 methyltransferase.The homologue of the EZH2 gene, EZH1, has similar enzymatic activity and, depending on the cell, the two components have different roles in controlling PRC2 function The roles of the two components in controlling PRC2 function are different depending on the cell. To date, no mutations or alterations in EZH1 expression have been found in human malignancies. In contrast, wild-type EZH2 expression is common in a variety of epithelial malignancies, and increased EZH2 expression has been shown to be due, at least in part, to transcriptional repression of specific microRNAs including Mir-101. Recently, the effect of somatic heterozygous EZH2 activating mutations on the Y641 locus has been confirmed in germinal center-mass B-cell lymphomas. Although the biological impact of activating lymphoma EZH2 mutations is not well understood, biochemical studies have shown that the Y641 locus increases methylation and dimethylation of H3K27, regardless of impaired monomethylated function of H3K27. Finally, PRC2-mediated transcriptional repression has also been recently identified as an important causative agent of promyelocytic leukemia (APL).