Diagnostic Use
L-asparaginase (L-ASNase) is used in the treatment of acute lymphoblastic leukaemia (ALL). Asparaginase catalysis the reaction of asparagine to aspartic acid and ammonia, which depletes asparagine from the circulation. Asparagine (Asn) is a non-essential amino acid and can be synthesized from aspartic acid by asparagine synthetase in healthy cells, or obtained from the diet, see Figure 1. However, insufficient levels of cellular asparagine lead to reduced DNA, RNA and protein synthesis; inhibition of cell growth; and ultimately the activation of apoptotic cell-death mechanisms. L-ASNase is also known to catalyse the hydrolysis of glutamine (Glu) to glutamic acid, resulting in depletion of circulating levels of this amino acid which is required for DNA and RNA synthesis in dividing cells.
Leukemic lymphoblasts (and certain other tumour cells) lack or have very low levels of L-asparagine synthetase so are unable to synthesize L-asparagine de novo and rely on supply from serum. Hence, depletion of circulating L-Asn by L-ASNase leads to cellular depletion in leukemic cells. This disrupts the proliferation of lymphoblasts and induces apoptosis. As normal cells have the ability to synthesize L-asparagine de novo via induction of the enzyme L-asparagine synthetase they are not affected by L-ASNas
Therapeutic drug monitoring is essential for optimising dosing schedules of different asparaginase preparations with respect to efficacy and tolerability; identifying patients with silent activation who require a change of asparaginase preparation; and identifying patients with pseudo-allergic reactions who can continue their asparaginase therapy.
Laboratory Handling
Separating
Aliquot to Specialist Biochemistry - Freezer
Laboratory
Freeze plasma on arrival in laboratory
