Human L-asparaginase: Acquiring knowledge of its activation (Review)

L-asparaginase enzymes have been a vital component of acute lymphoblastic leukemia therapy for >40 years. L-asparaginase acts by depleting plasma L-asparagine, which is essential to the survival of leukemia cells. In contrast to normal cells, tumor cells cannot synthesize L-asparagine and thus depend on its external uptake for growth. Currently, three bacterial L-asparaginases are used in therapy; however, they are associated with severe side-effects related to high toxicity and immunogenicity. The introduction of human L-asparaginase-like protein 1 in acute lymphoblastic leukemia treatment would avoid the problems caused by the bacterial enzymes; however, a major difficulty in the therapeutic use of the human enzyme comes from the fact that human L-asparaginase must be activated through an autoprocessing step, which is a low-efficiency process in vitro that results in reduced enzymatic activity. The present review article aimed to contribute to the understanding of the enzyme self-activation process and focuses on the efforts made for the development of a therapeutic variant of human L-asparaginase.

Automated summary

L-asparaginase enzymes have been crucial in acute lymphoblastic leukemia therapy for over 40 years by depleting plasma L-asparagine essential for leukemia cell survival. While bacterial enzymes used in therapy have severe side-effects, efforts are focused on developing a therapeutic variant of human L-asparaginase to avoid these problems.