L-asparaginase
Meaning of L-asparaginase: A bacterial enzyme pressed into service as a drug, exploiting one thing leukemia cells cannot do that healthy cells can.
Definition of L-asparaginase
L-asparaginase is an enzyme, taken from bacteria and given by injection, that destroys the amino acid asparagine circulating in the blood. Normal cells make their own supply and carry on. The cells of acute lymphoblastic leukemia largely cannot, so they run short of a building block they need for protein and die. It is a core part of treatment for that leukemia.
Why does it harm the leukemia and spare the rest?
Most cells carry an enzyme that builds asparagine from other materials, so emptying the blood of it changes nothing for them. Lymphoblasts, the immature cells that multiply in this leukemia, make very little of that enzyme and rely on what the blood delivers. Removing the supply leaves them unable to assemble proteins at the rate their own division demands, and they die. It is one of the clearest examples in cancer treatment of a difference in metabolism being used as a target, rather than an attack on dividing cells in general. The enzyme also degrades a second amino acid, glutamine, more slowly, which adds to its effects and to its toxicity.
Why are its side effects unlike other chemotherapy?
Because it is a bacterial protein rather than a small manufactured molecule. The immune system recognizes it as foreign, so allergic reactions are the signature problem, and antibodies can also clear the enzyme silently without any visible reaction, which is why its activity in blood is measured. Blocking protein production hits the liver hardest, lowering clotting factors and the natural anticoagulants together, so both bleeding and clots can follow, including clots in the veins draining the brain. Inflammation of the pancreas and high blood sugar are recognized. What it does not do is flatten the bone marrow or cause hair loss, which sets it apart from almost every drug it is given alongside.
What are the different preparations?
| Preparation | Source | Position |
|---|---|---|
| Native enzyme | Escherichia coli | Short acting, largely superseded |
| Pegylated form | The same enzyme with a polymer attached | Longer acting, fewer injections |
| Erwinia enzyme | A different bacterium | Used after allergy to the coli form |
Antibodies raised against one bacterial source do not recognize the other, which is what makes the switch possible. Peg-asparaginase has become the usual starting choice in acute lymphoblastic leukemia. The same enzyme also appears in regimens for lymphoblastic lymphoma and for an aggressive lymphoma of the nose and throat.
Also known as
Used in a sentence
L-asparaginase was omitted from the cycle after an allergic reaction.
Good to know
Unlike most drugs given with it, this enzyme does not suppress the bone marrow or cause hair loss, and its distinctive risks are allergy, clotting disturbance and inflammation of the pancreas.