Project 466988

The most common cancer in children is Acute Lymphoblastic Leukemia, or ALL. The cancer cells in ALL cannot make the amino acid asparagine. Instead, the cells get asparagine from the blood. We treat ALL patients with a drug that destroys asparagine in the blood, called asparaginase. When there is no asparagine, the cancer cells die. But how much drug is enough to give to patients? Where does the asparagine in the blood come from? We dont have the answers, so patients are getting more drug than necessary, and experience side effects. We are doing experiments in mice that will help understand whether the diet is a source of asparagine and whether bacteria in the intestines are another source. We will give mice diets with either a lot of asparagine or no asparagine and then give them the drug asparaginase. We will look at their blood and poop to see if there is a difference between the mice on different diets, before and after giving them asparaginase. Asparagine flooding into the blood from the diet or bacteria in the intestines could overwhelm the drug. If true, reducing levels of asparagine in the diet or altering the bacteria that make asparagine, could allow for lower doses of the drug. The ultimate objective is to know whether asparagine from the intestine, whether from diet or bacteria, directly affects blood levels of asparagine and therefore the amount of drug that may be necessary to treat ALL.