An intact gut microbiome protects genetically predisposed mice against leukemia
Open accessAbstract
The majority of childhood leukemias are precursor B-cell acute lymphoblastic leukemias (pB-ALLs) caused by a combination of prenatal genetic predispositions and oncogenic events occurring after birth. Although genetic predispositions are frequent in children (>1% to 5%), fewer than 1% of genetically predisposed carriers will develop pB-ALL. Although infectious stimuli are believed to play a major role in leukemogenesis, the critical determinants are not well defined. Here, by using murine models of pB-ALL, we show that microbiome disturbances incurred by antibiotic treatment early in life were sufficient to induce leukemia in genetically predisposed mice, even in the absence of infectious stimuli and independent of T cells. By using V4 and full-length 16S ribosomal RNA sequencing of a series of fecal samples, we found that genetic predisposition to pB-ALL (Pax5 heterozygosity or ETV6-RUNX1 fusion) shaped a distinct gut microbiome. Machine learning accurately (96.8%) predicted genetic predisposition using 40 of 3983 amplicon sequence variants as proxies for bacterial species. Transplantation of either wild-type (WT) or Pax5+/- hematopoietic bone marrow cells into WT recipient mice revealed that the microbiome is shaped and determined in a donor genotype-specific manner. Gas chromatography-mass spectrometry (GC-MS) analyses of sera from WT and Pax5+/- mice demonstrated the presence of a genotype-specific distinct metabolomic profile. Taken together, our data indicate that it is a lack of commensal microbiota rather than the presence of specific bacteria that promotes leukemia in genetically predisposed mice. Future large-scale longitudinal studies are required to determine whether targeted microbiome modification in children predisposed to pB-ALL could become a successful prevention strategy.
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An intact gut microbiome is necessary to prevent leukemia progression in genetically predisposed mice.
“However, an intact gut microbiome was later shown to be necessary to prevent leukemia progression in genetically predisposed mice (92).”
From The microbiome and human cancer (2021) · cites this paper as [92]
In blood cancers, preclinical data point to a delicate balance in which antibiotics or gut bacterial translocation can drive leukemic progression in hosts with genetic predisposition.
“In hematologic malignancies, preclinical evidence suggests a careful balance, where either antibiotics or gut bacterial translocation can trigger leukemic progression in genetically-predisposed hosts (47, 92).”
From The microbiome and human cancer (2021) · cites this paper as [92]
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- Authors
- Vicente-Dueñas, C., Janssen, S., Oldenburg, M., Auer, F., González-Herrero, I., Casado-García, A., Isidro-Hernández, M., Raboso-Gallego, J., Westhoff, P., Pandyra, A. A., Hein, D., Gössling, K. L., Alonso-López, D., De Las Rivas, J., Bhatia, S., García-Criado, F. J., García-Cenador, M. B., Weber, A. P. M., Köhrer, K., Hauer, J., Fischer, U., Sánchez-García, I., & Borkhardt, A.
- Affiliations
- Institute for Biomedical Research of Salamanca (IBSAL), Salamanca, Spain;
- Justus-Liebig-Universität Gießen (DE)
- Heinrich Heine University Düsseldorf (DE)
- German Cancer Research Center (DE)
- Consejo Superior de Investigaciones Científicas (ES)
- Cluster of Excellence on Plant Sciences (DE)
- Bioinformatics Unit, and
- National Center for Tumor Diseases (DE)
- Corresponding author
- Janssen, Stefan
- Oldenburg, Marina
- Fischer, Ute
- Borkhardt, Arndt
- ORCID
- Janssen, Stefan
- Oldenburg, Marina
- Auer, Franziska
- Casado-García, Ana
- Isidro-Hernández, Marta
- Raboso-Gallego, Javier
- Westhoff, Philipp
- Pandyra, Aleksandra A.
- Gössling, Katharina L.
- De Las Rivas, Javier
- Bhatia, Sanil
- García-Criado, Francisco Javier
- Weber, Andreas P. M.
- Köhrer, Karl
- Hauer, Julia
- Fischer, Ute
- Sánchez-García, Isidro
- Borkhardt, Arndt
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2020-10-29
- Volume
- 136
- Issue
- 18
- Pages
- 2003-2017
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC7694022
- OpenAlex
- W3086420584
- Cited by
- 106
- References
- 66
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 18 · 2023: 29 · 2022: 13 · 2021: 20 · 2020: 3
- FWCI
- 5.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Hispana (acceptedVersion, cc-by-nc-nd)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Gredos (University of Salamanca) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Keywords
- gut microbiota, pediatric leukemia, B-cell precursor acute lymphoblastic leukemia, genetic susceptibility, ETV6-RUNX1, commensal bacteria, leukemogenesis, bone marrow transplantation, microbiome-based prediction, leukemia prevention
- MeSH terms
- Gastrointestinal Microbiome, Animals, Disease Susceptibility, Feces, Female, Leukemia, Experimental, Mice, Inbred C57BL, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Mice, Knockout, Mice, PAX5 Transcription Factor, Dysbiosis
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