L-asparaginase as a critical component to combat Acute Lymphoblastic Leukaemia (ALL): A novel approach to target ALL

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• 作者：Usman Ali^a ; Muhammad Naveed^b ; Abid Ullah^a ; Khadija Ali^c ; Sayed Afzal Shah^e ; Shah Fahad^d ; Abdul Samad Mumtaz^e ; ^{asmumtaz@qau.edu.pk" class="auth_mail" title="E-mail the corresponding author} ; ^{samad207@yahoo.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：L-asparaginase ; Acute Lymphoblastic Leukaemia ; E. coli ; Blood plasma ; Anti-leukaemic drug ; Algae and plants
• 刊名：European Journal of Pharmacology
• 出版年：2016
• 出版时间：15 January 2016
• 年：2016
• 卷：771
• 期：Complete
• 页码：199-210
• 全文大小：638 K

文摘

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.