Language selection

Government of Canada / Gouvernement du Canada

Search

Gut bacterial gene changes following pegaspargase treatment in pediatric patients with acute lymphoblastic leukemia

From National Research Council Canada

DOIResolve DOI: https://doi.org/10.1080/10428194.2021.1953006
AuthorSearch for: ORCID identifier: https://orcid.org/0000-0002-9516-589X; Search for: ; Search for: ; Search for: ; Search for: ; Search for: ORCID identifier: https://orcid.org/0000-0001-5822-4371; Search for: ORCID identifier: https://orcid.org/0000-0002-6604-3009; Search for: ; Search for: ORCID identifier: https://orcid.org/0000-0002-1621-1772; Search for: 1; Search for: ; Search for:
Affiliation
  1. National Research Council of Canada. Human Health Therapeutics
FunderSearch for: NSHRF and JD Irving foundation; Search for: IWK Research Associateship
FormatText, Article
Subjectacute lymphoblastic leukemia; microbiome; pegaspargase; amino acid; pediatric
Abstract
Treatment of pediatric acute lymphoblastic leukemia (ALL) with pegaspargase exploits ALL cells dependency on asparagine. Pegaspargase depletes asparagine, consequentially affecting aspartate, glutamine and glutamate. The gut as a confounding source of these amino acids (AAs) and the role of gut microbiome metabolism of AAs has not been examined. We examined asparagine, aspartate, glutamine and glutamate in stool samples from patients over pegaspargase treatment. Microbial gene-products, which interact with these AAs were identified. Stool asparagine declined significantly, and 31 microbial genes changed over treatment. Changes were complex, and included genes involved in AA metabolism, nutrient sensing, and pathways increased in cancers. While we identified changes in a gene (iaaA) with limited asparaginase activity, it lacked significance after correction leaving open other mechanisms for asparagine decline, possibly including loss from gut to blood. Understanding pathways that change AA availability, including by microbes in the gut, could be useful in optimizing pegaspargase therapy.
Publication date
PublisherTaylor & Francis
In
  • Leukemia & Lymphoma 62, no. 13 (10 November 2021): 3244–3255.
LanguageEnglish
Peer reviewedYes
Export citationExport as RIS
Report a correctionReport a correction (opens in a new tab)
Record identifier377d1d25-30f5-4bd1-aca0-ee4671306751
Record created2023-01-18
Record modified2023-01-18
Date modified: