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

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.

Keywords:

• Acute lymphoblastic leukemia
• asparaginase treatment
• microbiome
• Bayesian model
• pediatric

Acknowledgements

The authors would like to thank participating children and their families, and the nurses at the IWK Health Centre for assistance with sample collection.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The 16S rRNA gene and metagenomic sequencing data used in this study are available under accession number PRJEB41463 at the European Nucleotide Archive.

Additional information

Funding

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.