title: L-asparaginase as a critical component to combat Acute Lymphoblastic Leukaemia (ALL): A novel approach to target ALL.
abstract: L-asparaginase, an anti-leukaemic drug that has been approved for clinical use for many years in the treatment of childhood Acute Lymphoblastic Leukaemia (ALL), is obtained from bacterial origin (Escherichia coli and Erwinia carotovora). The efficacy of L-asparaginase has been discussed for the past 40 years, and an ideal substitute for the enzyme has not yet been developed. The early clearance from plasma (short half-life) and requirement for multiple administrations and hence frequent physician visits make the overall treatment cost quite high. In addition, a high rate of allergic reactions in patients receiving treatment with the enzyme isolated from bacterial sources make its clinical application challenging. For these reasons, various attempts are being made to overcome these barriers. Therefore, the present article reviews studies focused on seeking substitutes for L-asparaginase through alternative sources including bacteria, fungi, actinomycetes, algae and plants to overcome these limitations. In addition, the role of chemical modifications and protein engineering approaches to enhance the drug's efficacy are also discussed. Moreover, an overview has also been provided in the current review regarding the contradiction among various researchers regarding the significance of the enzyme's glutaminase activity.
authors.affiliation: National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China.
authors.forename: Usman
authors.initials: U
authors.lastname: Ali
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Gujrat, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Naveed
authors.affiliation: National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China.
authors.forename: Abid
authors.initials: A
authors.lastname: Ullah
authors.affiliation: Department of Environmental Sciences, International Islamic University, Islamabad, Pakistan.
authors.forename: Khadija
authors.initials: K
authors.lastname: Ali
authors.affiliation: Department of Plant Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan.
authors.forename: Sayed Afzal
authors.initials: SA
authors.lastname: Shah
authors.affiliation: National Key Laboratory of Crop Genetic Improvement, MOA Key Laboratory of Crop Ecophysiology and Farming System in the Middle Reaches of the Yangtze River, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, PR China.
authors.forename: Shah
authors.initials: S
authors.lastname: Fahad
authors.affiliation: Department of Plant Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan. Electronic address: asmumtaz@qau.edu.pk.
authors.forename: Abdul Samad
authors.initials: AS
authors.lastname: Mumtaz
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001215:Asparaginase / Q000627:therapeutic use*; D055808:Drug Discovery; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D001215:Asparaginase
keywords: Acute Lymphoblastic Leukaemia; Algae and plants; Anti-leukaemic drug; Blood plasma; E. coli; L-asparaginase