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

Katherine A. Dunn; Zara Forbrigger; Jessica Connors; Mushfiqur Rahman; Alejandro Cohen; Johan Van Limbergen; Morgan G.I. Langille; Andrew W. Stadnyk; Joseph P. Bielawski; Susanne L. Penny; Tamara MacDonald; Ketan Kulkarni

doi:10.1080/10428194.2021.1953006

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

Katherine A. Dunn, Zara Forbrigger, Jessica Connors, Mushfiqur Rahman, Alejandro Cohen, Johan Van Limbergen, Morgan G.I. Langille, Andrew W. Stadnyk, Joseph P. Bielawski, Susanne L. Penny, Tamara MacDonald, Ketan Kulkarni

Medicine

Résultat de recherche: Article › examen par les pairs

2 Citations (Scopus)

Résumé

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.

Langue d'origine	English
Pages (de-à)	3244-3255
Nombre de pages	12
Journal	Leukemia and Lymphoma
Volume	62
Numéro de publication	13
DOI	https://doi.org/10.1080/10428194.2021.1953006
Statut de publication	Published - 2021

Note bibliographique

Funding Information:
This research was funded by a grant from NSHRF and JD Irving foundation to KK. KAD was funded by an IWK Research Associateship. The authors would like to thank participating children and their families, and the nurses at the IWK Health Centre for assistance with sample collection.

Publisher Copyright:
© 2021 Informa UK Limited, trading as Taylor & Francis Group.

ASJC Scopus Subject Areas

Hematology
Oncology
Cancer Research

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

ODD de l’ONU

Cette action contribue à la réalisation des objectifs de développement durable suivants

Accès au document

10.1080/10428194.2021.1953006

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Dunn, K. A., Forbrigger, Z., Connors, J., Rahman, M., Cohen, A., Van Limbergen, J., Langille, M. G. I., Stadnyk, A. W., Bielawski, J. P., Penny, S. L., MacDonald, T., & Kulkarni, K. (2021). Gut bacterial gene changes following pegaspargase treatment in pediatric patients with acute lymphoblastic leukemia. Leukemia and Lymphoma, 62(13), 3244-3255. https://doi.org/10.1080/10428194.2021.1953006

Dunn, KA, Forbrigger, Z, Connors, J, Rahman, M, Cohen, A, Van Limbergen, J, Langille, MGI , Stadnyk, AW , Bielawski, JP, Penny, SL, MacDonald, T & Kulkarni, K 2021, 'Gut bacterial gene changes following pegaspargase treatment in pediatric patients with acute lymphoblastic leukemia', Leukemia and Lymphoma, vol. 62, n° 13, pp. 3244-3255. https://doi.org/10.1080/10428194.2021.1953006

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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.",

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AU - Rahman, Mushfiqur

AU - Cohen, Alejandro

AU - Van Limbergen, Johan

AU - Langille, Morgan G.I.

AU - Stadnyk, Andrew W.

AU - Bielawski, Joseph P.

AU - Penny, Susanne L.

AU - MacDonald, Tamara

AU - Kulkarni, Ketan

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PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

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

Résumé

Note bibliographique

ASJC Scopus Subject Areas

PubMed: MeSH publication types

ODD de l’ONU

Accès au document

Autres fichiers et liens

Empreinte numérique

Citer