Factors determining therapeutic activity of L-asparaginase

Abstract

L-asparaginase (L-asp) is the basis of contemporary protocols used in the treatment of pediatric acute lymphoblastic leukemia and non-Hodgkin lymphomas. The key factor during L-asparaginase treatment is achieving sufficient serum activity of the drug during particular time period. There are several specified factors influencing L-asp activity. One is the preparation of the enzyme and their different pharmacokinetics. The other is L-asparaginase inactivation due to immunological response. The next factor, indirectly affecting L-asp activity, is the expression of asparagine synthetase, which is an enzyme of the opposite function to L-asparaginase.

The least known process is the enzymatic degradation of L-asparaginase by lisosomal cathepsin B and asparaginyl endopeptidase.