EZH2 in normal hematopoiesis and hematological malignancies.
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.
Institute of Human Genetics, CNRS UPR1142, Montpellier, France.
Laurie
L
Herviou
Institute of Human Genetics, CNRS UPR1142, Montpellier, France.
Giacomo
G
Cavalli
University of Montpellier 1, UFR de Médecine, Montpellier, France.|Department of Clinical Hematology, CHU Montpellier, Montpellier, France.
Guillaume
G
Cartron
Department of Biological Hematology, CHU Montpellier, Montpellier, France.|Institute of Human Genetics, CNRS UPR1142, Montpellier, France.|University of Montpellier 1, UFR de Médecine, Montpellier, France.
Bernard
B
Klein
Department of Biological Hematology, CHU Montpellier, Montpellier, France.|Institute of Human Genetics, CNRS UPR1142, Montpellier, France.|University of Montpellier 1, UFR de Médecine, Montpellier, France.
Jérôme
J
Moreaux
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D049109:Cell Proliferation; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005029:Ethylenediamines / Q000494:pharmacology; D005786:Gene Expression Regulation; D019337:Hematologic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008745:Methylation; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D057285:Precision Medicine; D011720:Pyrazoles / Q000494:pharmacology; D011728:Pyridones / Q000494:pharmacology
C000604935:EPZ011652; D005029:Ethylenediamines; C577920:GSK-2816126; D006657:Histones; D007211:Indoles; D011720:Pyrazoles; D011728:Pyridones; C048460:3-deazaneplanocin; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D000241:Adenosine
EZH2; Polycomb complex; hematological malignancies; therapeutic target