Investigating diet as a confounder to asparaginase treatment of acute lymphoblast leukemia

Abstract

Pegaspargase (P-ASP) is an integral part of the treatment of Acute Lymphoblastic Leukemia. P-ASP works by depleting serum asparagine (Asn), killing leukemic but not healthy cells. Whether confounding sources of Asn, for example, from diet and bacteria in the gut, impact the levels in blood has not been explored. We provided mice with an Asn rich (AR, 4%) or Asn depleted (AD, 0%) diet for 72 days prior to P-ASP injection. Neither diet change blood Asn levels. P-ASP depleted blood Asn in mice consuming either diet. In a second experiment, mice were provided with the diet one day prior to P-ASP injection. AD mice all had to be euthanized 3 days after injection due to an acute loss of weight. The remaining AR mice, despite also losing weight, completed the study; however, Asn levels were not depleted by P-ASP. The outcomes provide evidence that there may be an acute harmful effect of combing a diet lacking in Asn with Asn depletion by P-ASP. On the other hand, it is feasible that a diet high in Asn can overcome a single injection of P-ASP. Future studies should confirm these results, as well as include approaches to determine the source of Asn in the blood while ingesting diets with no or high amounts of Asn.