Epigenetic Regulators in the Development, Maintenance and Therapeutic Targeting of AML
- 1Tumor Initiation and Maintenance Program, Sanford Burnham Prebys Medical Discovery Institute (SBP), United States
The importance of epigenetic dysregulation to acute myeloid leukemia (AML) pathophysiology has become increasingly apparent in recent years. Epigenetic regulators including readers, writers, and erasers are recurrently dysregulated by way of chromosomal translocations, somatic mutations or genomic amplification in AML and many of these alterations are directly implicated in AML pathogenesis. Mutations in epigenetic regulators are often discovered in founder clones and persist after therapy, indicating that they may contribute to a premalignant state poised for the acquisition of cooperating mutations and frank malignancy. Apart from the proto-oncogenic impact of these mutations, the AML epigenome is also shaped by other epigenetic factors that are not mutated but co-opted by AML oncogenes, presenting with actionable vulnerabilities in this disease. Targeting the AML epigenome might also be important for eradicating AML leukemia stem cells (LSCs), which can be critical for disease maintenance and resistance to therapy. In this review, we describe the importance of epigenetic regulators in AML. We also summarize evidence implicating specific epigenetic regulators in AML pathobiology, and discuss emerging epigenome-based therapies for the treatment of AML in the clinic.
Keywords: Acute Myeloid Leukemia, epigenetic therapy, Leukemia stem cell, AML, epigenome, chromatin modification
Received: 16 Oct 2017;
Accepted: 07 Feb 2018.
Edited by:Keisuke Ito, Albert Einstein College of Medicine, United States
Reviewed by:Myriam Alcalay, Istituto Europeo di Oncologia, Italy
Takaomi Sanda, National University of Singapore, Singapore
Copyright: © 2018 Deshpande, Sun and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Aniruddha Deshpande, Sanford Burnham Prebys Medical Discovery Institute (SBP), Tumor Initiation and Maintenance Program, 10901 N Torrey Pines Road, San Diego, 10901 N Torrey Pines Road, La Jolla, 92037, California, United States, firstname.lastname@example.org