Pharmacogenetics of Asparaginase in Acute Lymphoblastic Leukemia

Overview

Journal Cancer Drug Resist

Date 2022 May 18

PMID 35582721

Authors

Rachid Abaji

Maja Krajinovic

Affiliations

Soon will be listed here.

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.

Citing Articles

Unraveling the Genetic Heterogeneity of Acute Lymphoblastic Leukemia Based on NGS Applications.

Ramirez Maldonado V, Navas Acosta J, Maldonado Marcos I, Villaverde Ramiro A, Hernandez-Sanchez A, Hernandez Rivas J Cancers (Basel). 2024; 16(23).

PMID: 39682152 PMC: 11639785. DOI: 10.3390/cancers16233965.

Asparaginase-associated Pancreatitis Complicated by Pancreatic Fluid Collection Treated with Endoscopic Cistogastrostomy in Pediatric Acute Lymphoblastic Leukemia: A Case Report and Systematic Review of the Literature.

Fiumana G, Pancaldi A, Bertani H, Boarino V, Cellini M, Iughetti L Clin Hematol Int. 2024; 5(4):51-61.

PMID: 38817959 PMC: 10742384. DOI: 10.46989/001c.90958.

Probing the active site of Class 3 L-asparaginase by mutagenesis. I. Tinkering with the zinc coordination site of ReAV.

Pokrywka K, Grzechowiak M, Sliwiak J, Worsztynowicz P, Loch J, Ruszkowski M Front Chem. 2024; 12:1381032.

PMID: 38638878 PMC: 11024299. DOI: 10.3389/fchem.2024.1381032.

Evaluating the Frequencies of , and Variant Alleles and Their Association with L-Asparaginase Hypersensitivity in Pediatric Acute Lymphoblastic Leukemia in Addis Ababa, Ethiopia.

Ali A, Adam H, Hailu D, Howe R, Abula T, Coenen M Appl Clin Genet. 2023; 16:131-137.

PMID: 37551203 PMC: 10404408. DOI: 10.2147/TACG.S404695.

"Pharmacogenetics of Cancer" - special issue.

Mini E, Nobili S Cancer Drug Resist. 2022; 3(2):225-231.

PMID: 35582607 PMC: 9090591. DOI: 10.20517/cdr.2020.10.

References

Asselin B, Ryan D, Frantz C, Bernal S, Leavitt P, Sallan S . In vitro and in vivo killing of acute lymphoblastic leukemia cells by L-asparaginase. Cancer Res. 1989; 49(15):4363-8. View

Larsen E, Devidas M, Chen S, Salzer W, Raetz E, Loh M . Dexamethasone and High-Dose Methotrexate Improve Outcome for Children and Young Adults With High-Risk B-Acute Lymphoblastic Leukemia: A Report From Children's Oncology Group Study AALL0232. J Clin Oncol. 2016; 34(20):2380-8. PMC: 4981974. DOI: 10.1200/JCO.2015.62.4544. View

Marshall G, Dalla Pozza L, Sutton R, Ng A, de Groot-Kruseman H, van der Velden V . High-risk childhood acute lymphoblastic leukemia in first remission treated with novel intensive chemotherapy and allogeneic transplantation. Leukemia. 2013; 27(7):1497-503. DOI: 10.1038/leu.2013.44. View

Krejci O, Starkova J, Otova B, Madzo J, Kalinova M, Hrusak O . Upregulation of asparagine synthetase fails to avert cell cycle arrest induced by L-asparaginase in TEL/AML1-positive leukaemic cells. Leukemia. 2004; 18(3):434-41. DOI: 10.1038/sj.leu.2403259. View

Sobczynska-Tomaszewska A, Bak D, Oralewska B, Oracz G, Norek A, Czerska K . Analysis of CFTR, SPINK1, PRSS1 and AAT mutations in children with acute or chronic pancreatitis. J Pediatr Gastroenterol Nutr. 2006; 43(3):299-306. DOI: 10.1097/01.mpg.0000232570.48773.df. View

Gervasini G, Vagace J . Impact of genetic polymorphisms on chemotherapy toxicity in childhood acute lymphoblastic leukemia. Front Genet. 2012; 3:249. PMC: 3504364. DOI: 10.3389/fgene.2012.00249. View

Zhang G, Nebert D . Personalized medicine: Genetic risk prediction of drug response. Pharmacol Ther. 2017; 175:75-90. PMC: 5653378. DOI: 10.1016/j.pharmthera.2017.02.036. View

Mei Y, Gao C, Wang K, Cui L, Li W, Zhao X . Effect of microRNA-210 on prognosis and response to chemotherapeutic drugs in pediatric acute lymphoblastic leukemia. Cancer Sci. 2014; 105(4):463-72. PMC: 4317805. DOI: 10.1111/cas.12370. View

Place A, Stevenson K, Vrooman L, Harris M, Hunt S, OBrien J . Intravenous pegylated asparaginase versus intramuscular native Escherichia coli L-asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCI 05-001): a randomised, open-label phase 3 trial. Lancet Oncol. 2015; 16(16):1677-90. DOI: 10.1016/S1470-2045(15)00363-0. View

10.

Chen S, Pei D, Yang W, Cheng C, Jeha S, Cox N . Genetic variations in GRIA1 on chromosome 5q33 related to asparaginase hypersensitivity. Clin Pharmacol Ther. 2010; 88(2):191-6. PMC: 3000799. DOI: 10.1038/clpt.2010.94. View

11.

Hojfeldt S, Wolthers B, Tulstrup M, Abrahamsson J, Gupta R, Harila-Saari A . Genetic predisposition to PEG-asparaginase hypersensitivity in children treated according to NOPHO ALL2008. Br J Haematol. 2018; 184(3):405-417. DOI: 10.1111/bjh.15660. View

12.

Conter V, Valsecchi M, Parasole R, Putti M, Locatelli F, Barisone E . Childhood high-risk acute lymphoblastic leukemia in first remission: results after chemotherapy or transplant from the AIEOP ALL 2000 study. Blood. 2014; 123(10):1470-8. DOI: 10.1182/blood-2013-10-532598. View

13.

Friedman R, Farh K, Burge C, Bartel D . Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 2008; 19(1):92-105. PMC: 2612969. DOI: 10.1101/gr.082701.108. View

14.

Pui C, Mullighan C, Evans W, Relling M . Pediatric acute lymphoblastic leukemia: where are we going and how do we get there?. Blood. 2012; 120(6):1165-74. PMC: 3418713. DOI: 10.1182/blood-2012-05-378943. View

15.

Sugimoto K, Suzuki H, Fujimura T, Ono A, Kaga N, Isobe Y . A clinically attainable dose of L-asparaginase targets glutamine addiction in lymphoid cell lines. Cancer Sci. 2015; 106(11):1534-43. PMC: 4714686. DOI: 10.1111/cas.12807. View

16.

Lopez-Santillan M, Iparraguirre L, Martin-Guerrero I, Gutierrez-Camino A, Garcia-Orad A . Review of pharmacogenetics studies of L-asparaginase hypersensitivity in acute lymphoblastic leukemia points to variants in the GRIA1 gene. Drug Metab Pers Ther. 2017; 32(1):1-9. DOI: 10.1515/dmpt-2016-0033. View

17.

Aslanian A, Kilberg M . Multiple adaptive mechanisms affect asparagine synthetase substrate availability in asparaginase-resistant MOLT-4 human leukaemia cells. Biochem J. 2001; 358(Pt 1):59-67. PMC: 1222032. DOI: 10.1042/0264-6021:3580059. View

18.

Pui C, Evans W . A 50-year journey to cure childhood acute lymphoblastic leukemia. Semin Hematol. 2013; 50(3):185-96. PMC: 3771494. DOI: 10.1053/j.seminhematol.2013.06.007. View

19.

Nguyen H, Su Y, Zhang J, Antanasijevic A, Caffrey M, Schalk A . A Novel l-Asparaginase with low l-Glutaminase Coactivity Is Highly Efficacious against Both T- and B-cell Acute Lymphoblastic Leukemias . Cancer Res. 2018; 78(6):1549-1560. PMC: 5856643. DOI: 10.1158/0008-5472.CAN-17-2106. View

20.

Castro-Pastrana L, Ghannadan R, Rieder M, Dahlke E, Hayden M, Carleton B . Cutaneous adverse drug reactions in children: an analysis of reports from the Canadian Pharmacogenomics Network for Drug Safety (CPNDS). J Popul Ther Clin Pharmacol. 2011; 18:e106-20. View