Page 104 - Read Online

Abaji et al. Cancer Drug Resist 2019;2:242-55 Cancer
DOI: 10.20517/cdr.2018.24 Drug Resistance

Review Open Access

Pharmacogenetics of asparaginase in acute
lymphoblastic leukemia

Rachid Abaji , Maja Krajinovic 1,2,3
1,2
1 Charles Bruneau Cancer Centre, Research Center, CHU Sainte-Justine, University of Montreal, Montreal, QC H3T 1C5, Canada.
2 Department of Pharmacology & Physiology, University of Montreal, Montreal, QC H3C 3J7, Canada.
3 Department of Pediatrics, University of Montreal, Montreal, QC H3T 1C5, Canada.

Correspondence to: Prof. Maja Krajinovic, Departments of Pediatrics and Pharmacology, University of Montreal & Research
Center, CHU Sainte-Justine, 3175 chemin de la Côte-Ste-Catherine, Montreal, QC H3T 1C5, Canada.
E-mail: maja.krajinovic@umontreal.ca

How to cite this article: Abaji R, Krajinovic M. Pharmacogenetics of asparaginase in acute lymphoblastic leukemia. Cancer
Drug Resist 2019;2:242-55. http://dx.doi.org/10.20517/cdr.2018.24

Received: 8 Nov 2018 First Decision: 12 Nov 2018 Revised: 21 Jan 2019 Accepted: 21 Feb 2019 Published: 19 Jun 2019

Science Editor: Enrico Mini Copy Editor: Cai-Hong Wang Production Editor: Huan-Liang Wu

Abstract
Asparaginase is a key component in leukemias and lymphomas treatment protocols and is suggested as a treatment
for other malignancies in which an amino acid depletion strategy is indicated. Asparaginase intolerance is subject to
inter-individual variability and can manifest as hypersensitivity reactions, pancreatitis, thrombosis, as well as metabolic
abnormalities, and may affect treatment outcome. Pharmacogenetics aims at enhancing treatment efficacy and safety by
better understanding the genetic basis of variability and its effect on the pharmacological responses. Many groups tried
to tackle the pharmacogenetics of asparaginase but the potential implementation of such findings remains debatable.
In this review, we highlight the most important findings reported in studies of the pharmacogenetics of asparaginase
related complications and treatment outcome in acute lymphoblastic leukemia.

Keywords: Asparaginase, pharmacogenomics, hypersensitivity reactions, pancreatitis, relapse, acute lymphoblastic
leukemia, adverse drug reactions

ASPARAGINASE AND ACUTE LYMPHOBLASTIC LEUKEMIA
L-asparaginase (ASNase) is a key component in leukemias and lymphomas treatment strategies and is
[1-4]
universally incorporated into major childhood acute lymphoblastic leukemia (ALL) treatment protocols .
ALL in adults has a much lower incidence than in children, and poor survival rates in this population pose

© 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