{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T16:29:34Z","timestamp":1788280174702,"version":"build-2803163510"},"reference-count":99,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzhen","doi-asserted-by":"publisher","award":["SZSM202011004"],"award-info":[{"award-number":["SZSM202011004"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>\n                    L-asparaginase, which hydrolyzes asparagine into aspartic acid and ammonia, is frequently used to treat acute lymphoblastic leukaemia in children. When combined with other chemotherapy drugs, the event-free survival rate is 90%. Due to immunogenicity and drug resistance, however, not all patients benefit from it, restricting the use of L-asparaginase therapy in other haematological cancers. To solve the problem of immunogenicity, several L-ASNase variants have emerged, such as\n                    <jats:italic>Erwinia<\/jats:italic>\n                    -ASNase and PEG-ASNase. However, even when\n                    <jats:italic>Erwinia<\/jats:italic>\n                    -ASNase is used as a substitute for\n                    <jats:italic>E. coli<\/jats:italic>\n                    -ASNase or PEG-ASNase, allergic reactions occur in 3%-33% of patients. All of these factors contributed to the development of novel L-ASNases. Additionally, L-ASNase resistance mechanisms, such as the methylation status of ASNS promoters and activation of autophagy, have further emphasized the importance of personalized treatment for paediatric haematological neoplasms. In this review, we discussed the metabolic effects of L-ASNase, mechanisms of drug resistance, applications in non-ALL leukaemia, and the development of novel L-ASNase.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2023.1070069","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T02:25:38Z","timestamp":1675218338000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["Possible mechanism of metabolic and drug resistance with L-asparaginase therapy in childhood leukaemia"],"prefix":"10.3389","volume":"13","author":[{"given":"Ruizhi","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianqi","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianwen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junbin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0900386","article-title":"Treating childhood acute lymphoblastic leukemia without cranial irradiation","volume":"12","author":"Pui","year":"2009","journal-title":"n Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25489","article-title":"L-asparaginase treatment in acute lymphoblastic leukemia: A focus on erwinia asparaginase","volume":"117","author":"Pieters","year":"2011","journal-title":"Cancer"},{"key":"B3","doi-asserted-by":"publisher","first-page":"62","DOI":"10.4103\/0976-500X.184769","article-title":"L-asparaginase in the treatment of patients with acute lymphoblastic leukemia","volume":"7","author":"Egler","year":"2016","journal-title":"J Pharmacol Pharmacother."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1084\/jem.98.6.565","article-title":"Regression of transplanted lymphomas induced in vivo by means of normal guinea pig serum. i. course of transplanted cancers of various kinds in mice and rats given guinea pig serum, horse serum, or rabbit serum","volume":"98","author":"Kidd","year":"1953","journal-title":"J Exp Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"5554","DOI":"10.4081\/hr.2014.5554","article-title":"Rationale for a pediatric-inspired approach in the adolescent and young adult population with acute lymphoblastic leukemia, with a focus on asparaginase treatment","volume":"6","author":"Rizzari","year":"2014","journal-title":"Hematol Rep"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1084\/jem.118.1.121","article-title":"Evidence that the l-asparaginase of guinea pig serum is responsible for its antilymphoma effects. 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