Role of HDACs in normal and malignant hematopoiesis

Normal hematopoiesis requires the accurate orchestration of lineage-specific patterns of gene expression at each stage of development, and epigenetic regulators play a vital role. Disordered epigenetic regulation has emerged as a key mechanism contributing to hematological malignancies. Histone deac...

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Vydané v:	Molecular cancer Ročník 19; číslo 1; s. 5 - 21
Hlavní autori:	Wang, Pan, Wang, Zi, Liu, Jing
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London BioMed Central 07.01.2020 BioMed Central Ltd Springer Nature B.V BMC
Predmet:	Aging Amino acids Animals Biomedical and Life Sciences Biomedicine Bone marrow Cancer Research Cell cycle Cell Differentiation Cofactors Deacetylation Deoxyribonucleic acid Development and progression DNA Drug development Drug resistance Enzymes Epigenesis, Genetic Epigenetic inheritance Epigenetics Etiology Gene expression Genes Genetic aspects Genetic transcription Granulocytes HDAC inhibitor Hematological malignancy Hematology Hematopoiesis Histone deacetylase Histone Deacetylase Inhibitors - therapeutic use Histone deacetylases Histone Deacetylases - chemistry Histone Deacetylases - metabolism Histones - genetics Histones - metabolism Homeostasis Humans Kinases Localization Lysine Molecular Targeted Therapy Mutation Neoplasms - drug therapy Neoplasms - enzymology Neoplasms - etiology Neoplasms - pathology Nonhistone proteins Oncology Physiological aspects Proteins Review Reviews Stem cells Therapeutic applications Transcription Transcription factors HDAC inhibitor Histone deacetylases Drug resistance Hematopoiesis Hematological malignancy
ISSN:	1476-4598, 1476-4598
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Shrnutí:	Normal hematopoiesis requires the accurate orchestration of lineage-specific patterns of gene expression at each stage of development, and epigenetic regulators play a vital role. Disordered epigenetic regulation has emerged as a key mechanism contributing to hematological malignancies. Histone deacetylases (HDACs) are a series of key transcriptional cofactors that regulate gene expression by deacetylation of lysine residues on histone and nonhistone proteins. In normal hematopoiesis, HDACs are widely involved in the development of various lineages. Their functions involve stemness maintenance, lineage commitment determination, cell differentiation and proliferation, etc. Deregulation of HDACs by abnormal expression or activity and oncogenic HDAC-containing transcriptional complexes are involved in hematological malignancies. Currently, HDAC family members are attractive targets for drug design, and a variety of HDAC-based combination strategies have been developed for the treatment of hematological malignancies. Drug resistance and limited therapeutic efficacy are key issues that hinder the clinical applications of HDAC inhibitors (HDACis). In this review, we summarize the current knowledge of how HDACs and HDAC-containing complexes function in normal hematopoiesis and highlight the etiology of HDACs in hematological malignancies. Moreover, the implication and drug resistance of HDACis are also discussed. This review presents an overview of the physiology and pathology of HDACs in the blood system.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23
ISSN:	1476-4598 1476-4598
DOI:	10.1186/s12943-019-1127-7