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

Eur J Pharmacol. 2016 Jan 15:771:199-210. doi: 10.1016/j.ejphar.2015.12.023. Epub 2015 Dec 15.

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.

Keywords: Acute Lymphoblastic Leukaemia; Algae and plants; Anti-leukaemic drug; Blood plasma; E. coli; L-asparaginase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Asparaginase / therapeutic use*
  • Drug Discovery
  • Humans
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*

Substances

  • Antineoplastic Agents
  • Asparaginase