[Histone modification and its application in therapy for hematologic malignancies -- review].
Histone modification is an important mechanism in oncogenesis and development of hematologic malignancies. Acetylation of lysine residues on histones and opening chromatin are correlated with activation of genes, whereas lysine residues methylation can result in either activation or repression on expressions of chromatin. The main point of all is deacetylation of histone mediated by histone deacetylases (HDACs). HDAC inhibitors are divided into 4 categories: short-chain fatty acids, hydroxamic acids, cyclic tetrapeptides and benzamides, owning different mechanisms in HDAC inhibition. Many kinds of I/II phase clinical tests showed that all these HDAC inhibitors have obviously therapeutic efficacies in treatment of hematologic malignancies with low poisons. Combination of HDAC inhibitors with DNA demethylation drugs can decrease DNA methylation, increase histone acetylation and recover antioncogene expression. As important parts of epigenetics, histone acetylation and HDAC inhibitors possess positive prospects in treatment of hematologic malignancies. In this review the advances of study on mechanisms of histone modification, HDAC inhibitors and their use in treatment of hematologic malignancies are summarized.
Fang
Ming-Hao
MH
Department Emergency Internal Medicine, Tongji Hospital, Huazhong University of Sciences and Technology Tongji Medical College, Wuhan, Hubei Province, China. fmhtj@hotmail.com
Ji
Xue-Mei
XM
D000107:Acetylation; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D006655:Histone Deacetylases / Q000235:genetics; D006657:Histones / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006655:Histone Deacetylases