L-asparaginase (Asparaginase (ASNase))

L-asparaginase is a hydrolase enzyme that catalyzes the hydrolysis of the amino acid L-asparagine to L-aspartic acid and ammonia, a reaction critical for its therapeutic action in acute lymphoblastic leukemia (ALL) and some lymphomas. Many hematological tumor cells rely on extracellular L-asparagine; depleting blood asparagine starves these cells, inhibiting protein synthesis and inducing cell death. L-asparaginase is most often produced using bacterial sources such as *Escherichia coli* or *Erwinia chrysanthemi*. Multiple pharmaceutical forms exist, including native (E. coli), pegylated forms (pegaspargase, calaspargase pegol), and recombinant products, each with unique dosing schedules, pharmacokinetics, and toxicity profiles. The main clinical use is as a key component of modern ALL therapy regimens, but notable safety risks include hypersensitivity reactions, hepatotoxicity, pancreatitis, and coagulopathies. Asparaginase therapy is guided by serum asparaginase activity (SAA), and immunogenicity monitoring may be required. Research is ongoing to improve the safety, immunogenicity, and pharmacokinetic properties of asparaginase by engineering new variants, including human-based forms.

Other names

L-asparaginaseASNaseL-asparagine amidohydrolaseEC 3.5.1.1

Depletes circulating L-asparagine, leading to inhibition of protein synthesis and apoptosis in asparagine-dependent tumor cells