Abstract
Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the Polycomb repressive complex 2, inhibits gene expression through methylation on lysine 27 of histone H3. EZH2 regulates normal hematopoietic stem cell self-renewal and differentiation. EZH2 also controls normal B cell differentiation. EZH2 deregulation has been described in many cancer types including hematological malignancies. Specific small molecules have been recently developed to exploit the oncogenic addiction of tumor cells to EZH2. Their therapeutic potential is currently under evaluation. This review summarizes the roles of EZH2 in normal and pathologic hematological processes and recent advances in the development of EZH2 inhibitors for the personalized treatment of patients with hematological malignancies.
Keywords:
EZH2; Polycomb complex; hematological malignancies; therapeutic target.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Adenosine / analogs & derivatives
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Adenosine / pharmacology
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B-Lymphocytes / cytology
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Cell Differentiation
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Cell Proliferation
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Enhancer of Zeste Homolog 2 Protein / antagonists & inhibitors*
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Enhancer of Zeste Homolog 2 Protein / metabolism*
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Epigenesis, Genetic
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Ethylenediamines / pharmacology
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Gene Expression Regulation
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Hematologic Neoplasms / drug therapy
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Hematologic Neoplasms / pathology*
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Hematopoiesis / physiology*
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Hematopoietic Stem Cells / cytology*
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Histones / metabolism
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Humans
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Indoles / pharmacology
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Methylation
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Polycomb Repressive Complex 2 / metabolism*
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Precision Medicine
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Pyrazoles / pharmacology
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Pyridones / pharmacology
Substances
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EPZ011652
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Ethylenediamines
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GSK-2816126
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Histones
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Indoles
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Pyrazoles
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Pyridones
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3-deazaneplanocin
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EZH2 protein, human
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Enhancer of Zeste Homolog 2 Protein
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Polycomb Repressive Complex 2
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Adenosine