Investigating the gut microbial community and genes in children with differing levels of change in serum asparaginase activity during pegaspargase treatment for acute lymphoblastic leukemia

Katherine A. Dunn; Jessica Connors; Joseph P. Bielawski; Jacob T. Nearing; Morgan G.I. Langille; Johan Van Limbergen; Conrad V. Fernandez; Tamara MacDonald; Ketan Kulkarni

doi:10.1080/10428194.2020.1850718

Investigating the gut microbial community and genes in children with differing levels of change in serum asparaginase activity during pegaspargase treatment for acute lymphoblastic leukemia

Katherine A. Dunn, Jessica Connors, Joseph P. Bielawski, Jacob T. Nearing, Morgan G.I. Langille, Johan Van Limbergen, Conrad V. Fernandez, Tamara MacDonald, Ketan Kulkarni

Medicine

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6 Citas (Scopus)

Resumen

Asparaginase (ASNase) is an effective treatment of pediatric acute lymphoblastic leukemia (ALL). Changes in ASNase activity may lead to suboptimal treatment and poorer outcomes. The gut microbiome produces metabolites that could impact ASNase therapy, however, remains uninvestigated. We examined gut-microbial community and microbial-ASNase and asparagine synthetase (ASNS) genes using 16SrRNA and metagenomic sequence data from stool samples of pediatric ALL patients. Comparing ASNase activity between consecutive ASNase-doses, we found microbial communities differed between decreased- and increased-activity samples. Escherichia predominated in the decreased-activity community while Bacteroides and Streptococcus predominated in the increased-activity community. In addition microbial ASNS was significantly (p=.004) negatively correlated with change in serum ASNase activity. These preliminary findings suggest microbial communities prior to treatment could affect serum ASNase levels, although the mechanism is unknown. Replication in an independent cohort is needed, and future research on manipulation of these communities and genes could prove useful in optimizing ASNase therapy.

Idioma original	English
Páginas (desde-hasta)	927-936
Número de páginas	10
Publicación	Leukemia and Lymphoma
Volumen	62
N.º	4
DOI	https://doi.org/10.1080/10428194.2020.1850718
Estado	Published - 2021

Nota bibliográfica

Funding Information:
This research was funded by a grant from Nova Scotia Health Research Foundation 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:
© 2020 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

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

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Dunn, K. A., Connors, J., Bielawski, J. P., Nearing, J. T., Langille, M. G. I., Van Limbergen, J., Fernandez, C. V., MacDonald, T., & Kulkarni, K. (2021). Investigating the gut microbial community and genes in children with differing levels of change in serum asparaginase activity during pegaspargase treatment for acute lymphoblastic leukemia. Leukemia and Lymphoma, 62(4), 927-936. https://doi.org/10.1080/10428194.2020.1850718

Investigating the gut microbial community and genes in children with differing levels of change in serum asparaginase activity during pegaspargase treatment for acute lymphoblastic leukemia. / Dunn, Katherine A.; Connors, Jessica; Bielawski, Joseph P. et al.
En: Leukemia and Lymphoma, Vol. 62, N.º 4, 2021, p. 927-936.

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

Dunn, KA, Connors, J, Bielawski, JP, Nearing, JT, Langille, MGI, Van Limbergen, J, Fernandez, CV, MacDonald, T & Kulkarni, K 2021, 'Investigating the gut microbial community and genes in children with differing levels of change in serum asparaginase activity during pegaspargase treatment for acute lymphoblastic leukemia', Leukemia and Lymphoma, vol. 62, n.º 4, pp. 927-936. https://doi.org/10.1080/10428194.2020.1850718

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abstract = "Asparaginase (ASNase) is an effective treatment of pediatric acute lymphoblastic leukemia (ALL). Changes in ASNase activity may lead to suboptimal treatment and poorer outcomes. The gut microbiome produces metabolites that could impact ASNase therapy, however, remains uninvestigated. We examined gut-microbial community and microbial-ASNase and asparagine synthetase (ASNS) genes using 16SrRNA and metagenomic sequence data from stool samples of pediatric ALL patients. Comparing ASNase activity between consecutive ASNase-doses, we found microbial communities differed between decreased- and increased-activity samples. Escherichia predominated in the decreased-activity community while Bacteroides and Streptococcus predominated in the increased-activity community. In addition microbial ASNS was significantly (p=.004) negatively correlated with change in serum ASNase activity. These preliminary findings suggest microbial communities prior to treatment could affect serum ASNase levels, although the mechanism is unknown. Replication in an independent cohort is needed, and future research on manipulation of these communities and genes could prove useful in optimizing ASNase therapy.",

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Investigating the gut microbial community and genes in children with differing levels of change in serum asparaginase activity during pegaspargase treatment for acute lymphoblastic leukemia

Resumen

Nota bibliográfica

ASJC Scopus Subject Areas

PubMed: MeSH publication types

ODS de las Naciones Unidas

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