Page 59 - Read Online

Meyer et al. Cancer Drug Resist 2019;2:313-25 Cancer
DOI: 10.20517/cdr.2019.11 Drug Resistance

Review Open Access

The epigenome in pediatric acute lymphoblastic
leukemia: drug resistance and therapeutic
opportunities

Lauren K. Meyer, Michelle L. Hermiston

Department of Pediatrics, University of California, San Francisco, CA 94143, USA.

Correspondence to: Dr. Michelle L. Hermiston, Department of Pediatrics, University of California, San Francisco, CA 94143, USA.
E-mail: michelle.hermiston@ucsf.edu

How to cite this article: Meyer LK, Hermiston ML. The Epigenome in Pediatric Acute Lymphoblastic Leukemia: Drug Resistance
and Therapeutic Opportunities. Cancer Drug Resist 2019;2:313-25. http://dx.doi.org/10.20517/cdr.2019.11
Received: 28 Feb 2019 First Decision: 28 Apr 2019 Revised: 6 May 2019 Accepted: 14 May 2019 Published: 19 Jun 2019

Science Editor: Aamir Ahmad Copy Editor: Cai-Hong Wang Production Editor: Huan-Liang Wu

Abstract
Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood. The genomic landscape of pediatric
ALL has been extensively characterized, allowing for the identification of distinct molecular subtypes of this disease. This
in turn has facilitated improvements in risk stratification and tailoring of therapy, resulting in dramatic improvements in
survival rates over the past several decades. However, despite these improvements, outcomes remain dismal for the ten
percent of patients who continue to fail therapy and relapse. Although the genetic landscape of pediatric ALL is well-
understood, increasing evidence suggests that genetic alterations alone are insufficient to promote leukemogenesis
and the acquisition of chemoresistance that leads to disease relapse. Instead, cooperating epigenetic alterations
are now recognized as important contributors to the aberrant gene expression profiles that are characteristic of the
molecular subtypes of ALL, and changes in the epigenetic landscape are now thought to underlie the development of
chemoresistance and ultimately disease relapse. This review article focuses on the expanding knowledge of the role of
the epigenome in ALL pathogenesis, progression, and response to therapy, and highlights preclinical and clinical efforts
to target the epigenome as a means of overcoming chemoresistance and improving outcomes for children with ALL.

Keywords: Acute lymphoblastic leukemia, methylation, histone modification, epigenetic modulator

INTRODUCTION
Acute lymphoblastic leukemia (ALL) is a malignancy of lymphoid progenitor cells of either the B- or T-cell
lineage. ALL is the most common malignancy of childhood, with B-cell ALL (B-ALL) accounting for 85%

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

www.cdrjournal.com