Epigenetics changes affecting L-asparaginase therapy in human leukemia: a mini review

Document Type : Original Article

Authors

Department of biology, Faculty of basic science, University of Sistan and Baluchestan, Zahedan, Iran

Abstract

ASNase (L-asparaginase), as an effective anticancer component, is used in chemotherapy and treatment of ALL (acute lymphoblastic leukemia) and natural killer (NK)/T-cell lymphoma. In contrary to significant efficiency of ASNase hypersensitivity or allergy is the most common asparaginase-associated toxicities in treatment of pediatric and adult, which leads termination of ASNase therapy in ALL patients. Additionally, resistance to treatment is another obstacle in ASNase therapy, which consequently ALL relapse is occurred in result of leukemic cells resistance to treatment. A reciprocal correlation between asparagine synthetase (ASNS) expression and sensitivity to ASNase treatment is reported in ALL cells, that ASNS levels may deactivate the ASNase therapy effects. Epigenetic changes besides genomic modulation, gene expression profiling alterations and genetic polymorphism have an effective role in ASNS expression and cellular resistance to ASNase consequently. Recent studies have shown DNA hypermethylation in ASNS promoter, which named as ‘silent inactivation’, prevents it’s transcriptional expression following asparagine depletion. So, epigenetic modifications influence chemotherapy response in ALL patients and have an impressive role in achieving new therapeutic approaches. In this review we focused on the known epigenetic changes in ASNS expression in ALL cells and also prospect to the epigenetic efficacy such as demethylating agents to combined treatment that could modulate the sensitivity and resistance to ASNase therapy in ALL patients.

Keywords


[1] Brumano LP, da Silva FVS, Costa-Silva TA, Apolinário AC, Santos JHPM, Kleingesinds EK, et al. Development of L-asparaginase biobetters: Current research status and review of the desirable quality profiles. Frontiers in Bioengineering and Biotechnology. 2019.
[2] Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J. 2017;
[3] Avramis VI. Asparaginases: Biochemical pharmacology and modes of drug resistance. Anticancer Research. 2012.
[4] Burke MJ. How to manage asparaginase hypersensitivity in acute lymphoblastic leukemia. Future Oncology. 2014.
[5] Serravalle S, Bertuccio SN, Astolfi A, Melchionda F, Pession A. Synergistic cytotoxic effect of l-asparaginase combined with decitabine as a demethylating agent in pediatric T-ALL, with specific epigenetic signature. Biomed Res Int. 2016;
[6] Batool T, Makky EA, Jalal M, Yusoff MM. A Comprehensive Review on l-Asparaginase and Its Applications. Applied Biochemistry and Biotechnology. 2016.
[7] Chien WW, Le Beux C, Rachinel N, Julien M, Lacroix CE, Allas S, et al. Differential mechanisms of asparaginase resistance in B-type acute lymphoblastic leukemia and malignant natural killer cell lines. Sci Rep. 2015;
[8] Avramis VI, Tiwari PN. Asparaginase (native ASNase or pegylated ASNase) in the treatment of acute lymphoblastic leukemia. International Journal of Nanomedicine. 2006.
[9] Banerji J. Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons (Review-Hypothesis). International Journal of Molecular Medicine. 2015.
[10] 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 Metabolism and Personalized Therapy. 2017.
[11] Yeang SH, Chan A, Tan CW, Lim ST, Ng HJ. Incidence and management of toxicity associated with L-asparaginase in the treatment of ALL and NK/T-cell lymphoma: An observational study. Asian Pacific J Cancer Prev. 2016;
 
[12] Stock W, Douer D, Deangelo DJ, Arellano M, Advani A, Damon L, et al. Prevention and management of asparaginase/pegasparaginase-associated toxicities in adults and older adolescents: Recommendations of an expert panel. Leuk Lymphoma. 2011;
[13] Krishnapura PR, Belur PD, Subramanya S. A critical review on properties and applications of microbial l-asparaginases. Critical Reviews in Microbiology. 2016.
[14] Jiang J, Srivastava S, Seim G, Pavlova NN, King B, Zou L, et al. Promoter demethylation of the asparagine synthetase gene is required for ATF4-dependent adaptation to asparagine depletion. J Biol Chem. 2019;
[15] Peng H, Shen N, Qian L, Sun XL, Koduru P, Goodwin LO, et al. Hypermethylation of CpG islands in the mouse asparagine synthetase gene: Relationship to asparaginase sensitivity in lymphoma cells. Partial methylation in normal cells. Br J Cancer. 2001;
[16] Chatterton Z, Morenos L, Mechinaud F, Ashley DM, Craig JM, Sexton-Oates A, et al. Epigenetic deregulation in pediatric acute lymphoblastic leukemia. Epigenetics. 2014;
[17] Andrade AF, Borges KS, Silveira VS. Update on the use of L-asparaginase in infants and adolescent patients with acute lymphoblastic leukemia. Clin Med Insights Oncol. 2014;
[18] Kyrtsonis MC, Maltezas D. New evidence of gene inactivation by aberrant DNA-Methylation in T-cell leukemia, with treatment implications. Leukemia Research. 2016.
[19] Nakamura A, Nambu T, Ebara S, Hasegawa Y, Toyoshima K, Tsuchiya Y, et al. Inhibition of GCN2 sensitizes ASNS-low cancer cells to asparaginase by disrupting the amino acid response. Proc Natl Acad Sci U S A. 2018;
[20] Moser SC, van der Eerden BCJ. Osteocalcin — A versatile bone-derived hormone. Front Endocrinol (Lausanne). 2019;10(JAN):4–9.
[21] Kafkewitz D, Bendich A. Enzyme-induced asparagine and glutamine depletion and immune system function. American Journal of Clinical Nutrition. 1983.
[22] Touzart A, Lengline E, Latiri M, Belhocine M, Smith C, Thomas X, et al. Epigenetic silencing affects L-asparaginase sensitivity and predicts outcome in T-ALL. Clin Cancer Res. 2019;
[23] Asselin BL, Frantz CN, Cohen HJ, Ryan D, Sallan SE, Bernal SD, et al. In Vitro and in Vivo Killing of Acute Lymphoblastic Leukemia Cells by L-Asparaginase1. Cancer Res. 1989;
[24] Alrumman SA, Mostafa YS, Al-izran KA, Alfaifi MY, Taha TH, Elbehairi SE. Production and Anticancer Activity of an L-Asparaginase from Bacillus licheniformis Isolated from the Red Sea, Saudi Arabia. Sci Rep. 2019;
[25] Narta UK, Kanwar SS, Azmi W. Pharmacological and clinical evaluation of l-asparaginase in the treatment of leukemia. Critical Reviews in Oncology/Hematology. 2007.
[26] Ueno T, Ohtawa K, Mitsui K, Kodera Y, Hiroto M, Matsushima A, et al. Cell cycle arrest and apoptosis of leukemia cells induced by L-asparaginase. Leukemia. 1997;
[27] Tanfous M Ben, Sharif-Askari B, Ceppi F, Laaribi H, Gagne V, Rousseau J, et al. Polymorphisms of asparaginase pathway and asparaginase-related complications in children with acute lymphoblastic leukemia. Clin Cancer Res. 2015;
[28] Akagi T, Yin D, Kawamata N, Bartram CR, Hofmann WK, Wolf I, et al. Methylation analysis of asparagine synthetase gene in acute lymphoblastic leukemia cells [8]. Leukemia. 2006.
[29] Iwamoto S, Mihara K, Downing JR, Pui CH, Campana D. Mesenchymal cells regulate the response of acute lymphoblastic leukemia cells to asparaginase. J Clin Invest. 2007;
[30] Kaspers GJL, Veerman AJP, Pieters R, Broekema GJ, Huismans DR, Kazemier KM, et al. Mononuclear cells contaminating acute lymphoblastic leukaemic samples tested for cellular drug resistance using the methyl-thiazol-tetrazolium assay. Br J Cancer. 1994;
[31] He B, Cathryn Hlavka-Zhang J, B. Lock R, Jing D. Epigenetic Landscape in Leukemia and Its Impact on Antileukemia Therapeutics. In: Germ Line Mutations Associated Leukemia. 2019.
[32] Navarrete-Meneses M del P, Pérez-Vera P. Epigenetic alterations in acute lymphoblastic leukemia. Boletín Médico Del Hosp Infant México (English Ed. 2017;
[33] Dawson MA, Kouzarides T. Cancer epigenetics: From mechanism to therapy. Cell. 2012.
[34] Chatterton Z, Morenos L, Saffery R, Craig JM, Ashley D, Wong NC. DNA methylation and miRNA expression profiling in childhood B-cell acute lymphoblastic leukemia. Epigenomics. 2010.
[35] Garcia-Manero G, Yang H, Kuang SQ, O’Brien S, Thomas D, Kantarjian H. Epigenetics of Acute Lymphocytic Leukemia. Semin Hematol. 2009;
[36] San Jose-Eneriz E, Agirre X, Rodríguez-Otero P, Prosper F. Epigenetic regulation of cell signaling pathways in acute lymphoblastic leukemia. Epigenomics. 2013.
[37] Lomelino CL, Andring JT, McKenna R, Kilberg MS. Asparagine synthetase: Function, structure, and role in disease. Journal of Biological Chemistry. 2017.
[38] Su N, Pan YX, Zhou M, Harvey RC, Hunger SP, Kilberg MS. Correlation between asparaginase sensitivity and asparagine synthetase protein content, but not mRNA, in acute lymphoblastic leukemia cell lines. Pediatr Blood Cancer. 2008;
[39] Holleman A, Cheok MH, Den Boer ML, Yang W, Veerman AJP, Kazemier KM, et al. Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment. N Engl J Med. 2004;
[40] Karsenty G, Kousteni S. Bone as an endocrine organ. Encycl Endocr Dis. 2018;18(5):47–51.
[41] Ding Y, Li Z, Broome JD. Epigenetic changes in the repression and induction of asparagine synthetase in human leukemic cell lines. Leukemia. 2005;
[42] Stams WAG, Den Boer ML, Holleman A, Appel IM, Beverloo HB, Van Wering ER, et al. Asparagine synthetase expression is linked with L-asparaginase resistance in TEL-AML1-negative but not TEL-AML1-positive pediatric acute lymphoblastic leukemia. Blood. 2005;
[43] Stams WAG, Den Boer ML, Beverloo HB, Meijerink JPP, Stigter RL, Van Wering ER, et al. Sensitivity to L-asparaginase is not associated with expression levels of asparagine synthetase in t(12;21)+ pediatric ALL. Blood. 2003;
[44] Krall AS, Xu S, Graeber TG, Braas D, Christofk HR. Asparagine promotes cancer cell proliferation through use as an amino acid exchange factor. Nat Commun. 2016;
[45] Grobbelaar C, Ford AM. The Role of MicroRNA in Paediatric Acute Lymphoblastic Leukaemia: Challenges for Diagnosis and Therapy. Journal of Oncology. 2019.
[46] Schotte D, de Menezes RX, Moqadam FA, Khankahdani LM, Lange-Turenhout E, Chen C, et al. MicroRNA characterize genetic diversity and drug resistance in pediatric acute lymphoblastic leukemia. Haematologica. 2011;