Bacterial Heat Shock Protein Genes During Induction Chemotherapy In Pediatric Patients with Acute Lymphoblastic Leukemia

Abstract

Background: Heat shock proteins (HSP) protect cancer cells. Gastrointestinal bacteria contain HSP genes and can release extracellular vesicles which act as biological shuttles. Stress from treatment may result in a microbial community with more HSP genes, which could contribute to circulating HSP levels. Methods: The authors examined the abundance of five bacterial HSP genes pre-treatment and during induction in stool sequences from 30 pediatric acute lymphoblastic leukemia patients. Results: Decreased mean HTPG counts (p = 0.0024) pre-treatment versus induction were observed. During induction, HTPG, Shannon diversity and Bacteroidetes decreased (p = 7.5e-4; 1.1e–3; 8.6e-4), while DNAK and Firmicutes increased (p = 6.9e-3; 9.2e-4). Conclusion: Understanding microbial HSP gene community changes with treatment is the first step in determining if bacterial HSPs are important to the tumor microenvironment and leukemia treatment.

Keywords::

• acute lymphoblastic leukemia
• bacteroidetes
• chemotherapy
• DNAK
• firmicutes
• heat shock protein genes
• heat shock proteins
• HSP70
• HSP90
• HTPG
• microbiome
• pediatric

Author contributions

KA Dunn, T MacDonald and K Kulkarni contributed to the conception and design of the study. KA Dunn and E MacDonald performed analyses. KA Dunn wrote the manuscript. All authors secured funding for the project and read and approved the submitted version.

Acknowledgments

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

Financial disclosure

This research was funded by a Nova Scotia Health Research Foundation (now Research Nova Scotia) establishment grant, Beatrice Hunter Health Research Institute New Investigator grant and JD Irving Foundation grant to K Kulkarni. KA Dunn was funded in part by an IWK Research Associateship and a Weston Foundation Grant. E MacDonald was funded by an IWK summer research award. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, stock ownership or options and expert testimony.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This research was funded by a Nova Scotia Health Research Foundation (now Research Nova Scotia) establishment grant, Beatrice Hunter Health Research Institute New Investigator grant and JD Irving Foundation grant to K Kulkarni. KA Dunn was funded in part by an IWK Research Associateship and a Weston Foundation Grant. E MacDonald was funded by an IWK summer research award. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.