Epigenetic therapies by targeting aberrant histone methylome in AML: molecular mechanisms, current preclinical and clinical development

• Published in: Oncogene Vol. 36; no. 13; pp. 1753 - 1759
• Main Authors: Tsai, C T, So, C W E
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.03.2017; Nature Publishing Group
• Subjects: 631/154/555; Acetylation; Acute myelocytic leukemia; Analysis; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; Care and treatment; Cell Biology; Clinical Studies as Topic; DNA methylation; DNA Methylation - drug effects; Drug Evaluation, Preclinical; Enzymes; Epigenesis, Genetic - drug effects; Epigenetic inheritance; Epigenetics; Gene expression; Gene therapy; Genetic aspects; Health aspects; Histone Demethylases - antagonists & inhibitors; Histone Demethylases - metabolism; Histone Methyltransferases; Histone-Lysine N-Methyltransferase - antagonists & inhibitors; Histone-Lysine N-Methyltransferase - metabolism; Histones - metabolism; Human Genetics; Humans; Internal Medicine; Leukemia; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - metabolism; Medicine; Medicine & Public Health; Molecular Targeted Therapy; Oncology; Protein Binding; Review; Risk factors; Signal Transduction - drug effects; Treatment Outcome; United Kingdom
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2016.315

While the current epigenetic drug development is still largely restricted to target DNA methylome, emerging evidence indicates that histone methylome is indeed another major epigenetic determinant for gene expression and frequently deregulated in acute myeloid leukaemia (AML). The recent advances in dissecting the molecular regulation and targeting histone methylome in AML together with the success in developing lead compounds specific to key histone methylation-modifying enzymes have revealed new opportunities for effective leukaemia treatment. In this article, we will review the emerging functions of histone methyltransferases and histone demethylases in AML, especially MLL-rearranged leukaemia. We will also examine recent preclinical and clinical studies that show significant promises of targeting these histone methylation-modifying enzymes for AML treatment.