Pharmacogenetics of asparaginase in acute lymphoblastic leukemia.

Rachid Abaji,Maja Krajinovic

doi:10.20517/cdr.2018.24

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.

Highlights

L-asparaginase (ASNase) is a key component in leukemias and lymphomas treatment strategies and is universally incorporated into major childhood acute lymphoblastic leukemia (ALL) treatment protocols[1,2,3,4]
This result was achieved by the creation and continuous optimization of multi-agent protocols through evidence based medicine, refined stratification of patients into risk groups, personalized chemotherapy that exploit the differences in the characteristics between host and leukemia cells, and improvement in supportive care[5,12,13,14]
This is the core goal of pharmacogenetics (PGx) which aims at enhancing treatment efficacy and safety by providing a better understanding of the genetic basis of variability and its effect on the pharmacological responses[14,16]

Summary

Introduction

L-asparaginase (ASNase) is a key component in leukemias and lymphomas treatment strategies and is universally incorporated into major childhood acute lymphoblastic leukemia (ALL) treatment protocols[1,2,3,4]. Another GWAS was performed on a cohort of 3,308 pediatric ALL patients treated according to St. Jude Children’s Research Hospital protocols or Children’s Oncology Group protocols and demonstrated that variants within genes regulating the immune response, genes involved in T-cell function, strongly influenced the risk of ASNase hypersensitivity.

Results

Conclusion