Epigenetic mechanisms underlying the therapeutic effects of HDAC inhibitors in chronic myeloid leukemia.

Abstract

Chronic myeloid leukemia (CML) is a hematological disorder caused by the oncogenic BCR-ABL fusion protein in more than 90% of patients. Despite the striking improvements in the management of CML patients since the introduction of tyrosine kinase inhibitors (TKis), the appearance of TKi resistance and side effects lead to treatment failure, justifying the need of novel therapeutic approaches. Histone deacetylase inhibitors (HDACis), able to modulate gene expression patterns and important cellular signaling pathways through the regulation of the acetylation status of both histone and non-histone protein targets, have been reported to display promising anti-leukemic properties alone or in combination with TKis. This review summarizes pre-clinical and clinical studies that investigated the mechanisms underlying the anticancer potential of HDACis and discusses the rationale for a combination of HDACis with TKis as a therapeutic option in CML.

• Authors: Manon Lernoux, Michael Schnekenburger, Mario Dicato, Marc Diederich
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 173 Pg. 113698 (03 2020) ISSN: 1873-2968 [Electronic] England
• PMID: 31706847 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Histone Deacetylase Inhibitors
• Protein Kinase Inhibitors
• Fusion Proteins, bcr-abl

Topics

• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Drug Resistance, Neoplasm (drug effects, genetics)
• Epigenesis, Genetic
• Fusion Proteins, bcr-abl (genetics)
• Gene Expression Profiling
• Gene Expression Regulation, Leukemic (drug effects)
• Histone Deacetylase Inhibitors (administration & dosage, therapeutic use)
• Humans
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (genetics)
• Protein Kinase Inhibitors (administration & dosage, therapeutic use)