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.