The researchers focused on RNA rather than DNA for several reasons. RNA is generally more indicative of recent microbial activity, since it is transcribed from active genes and degrades more quickly than DNA. In addition, a much larger portion of microbial genomes is transcribed into RNA, making it a richer analyte for detecting microbial presence. The team reasoned that these properties could make RNA a more sensitive and informative marker of circulating microbes than DNA, which had been the focus of earlier studies.

To conduct the analysis, the researchers used a large whole-transcriptome dataset from hundreds of patients with acute myeloid leukemia. The samples included blood and bone marrow specimens collected at diagnosis. The team applied stringent quality control measures to distinguish true microbial signals from artifacts, filtering out low-confidence classifications and removing taxa that were unlikely to be members of the human microbiome. They also compared their findings against healthy controls to ensure that the microbial signals were specific to leukemia patients.

The analysis revealed that bacterial RNA far outnumbered viral RNA in the samples, with bacterial reads dominating the circulating metatranscriptome. The researchers found that the overall microbial load varied considerably from patient to patient, and that this variation was not explained by differences in sample collection or processing. When they compared patients with high versus low microbial loads, they observed differences in the composition of the immune cell populations in the samples, suggesting a link between circulating microbes and the immune environment of the disease.

One of the most striking findings involved the relationship between microbial load and treatment response. The researchers found that patients with higher microbial loads tended to show differences in the expression of genes involved in immune pathways, including the complement cascade and the antibacterial response. They also observed that the abundance of specific microbial taxa correlated with the expression of genes involved in butyrate metabolism, a pathway that has been implicated in immune regulation and cancer progression.

The team also explored whether the microbial signals could predict response to specific therapies. They found that the abundance of certain taxa was associated with differences in the sensitivity of leukemia cells to a range of drugs, including agents that target the BCL-2 protein and other survival pathways. While the study did not establish a causal relationship between circulating microbes and drug response, the findings suggest that the circulating metatranscriptome may carry information relevant to therapeutic decision-making.

The researchers applied several statistical models to account for potential confounders, including differences in sequencing batch, age, and sample type. They also used permutation testing to assess the significance of their findings, ensuring that the observed associations were unlikely to arise by chance. The team emphasized that the study was exploratory in nature and that further work would be needed to validate the findings in independent cohorts.

The study has important implications for the field of cancer microbiome research. Earlier studies have reported microbial DNA in tumors and blood samples from cancer patients, but the field has been plagued by concerns about contamination and artifacts. The new study addresses these concerns by applying rigorous quality control measures and by focusing on RNA, which is less susceptible to contamination from environmental sources. The findings suggest that the circulating metatranscriptome may be a valuable and underexplored source of clinical information in leukemia.

The researchers also noted that their findings may have relevance beyond acute myeloid leukemia. The pathways implicated in the study, including immune regulation and butyrate metabolism, are involved in a range of cancers and inflammatory diseases. The team suggested that the circulating metatranscriptome may be a useful analyte in other cancers as well, and that further work should explore its potential in these settings.

The study represents an important step forward in the effort to understand the role of microbes in cancer. By focusing on RNA and by applying rigorous quality control measures, the researchers have provided a valuable resource for the field and have opened a new avenue for clinical investigation. The findings suggest that the circulating metatranscriptome may carry information relevant to treatment response and immune regulation, and that further work should explore its potential as a clinical tool in leukemia and beyond.

Subject of Research: Circulating microbial RNA in acute myeloid leukemia patients

Article Title: The circulating metatranscriptome in acute myeloid leukemia patients: an RNA-seq reanalysis

Article References: Nguyen, A. D. D., Kern, R., Dombrovski, T., & LaFramboise, T. (2026). The circulating metatranscriptome in acute myeloid leukemia patients: an RNA-seq reanalysis. Frontiers in Microbiomes, 5, Article 1903806. https://doi.org/10.3389/frmbi.2026.1903806

Image Credits: AI Generated

DOI: 10.3389/frmbi.2026.1903806

Keywords: acute myeloid leukemia, microbiome, metatranscriptome, RNA, treatment response, immune regulation, butyrate metabolism, cancer, blood, bone marrow, circulating, acute