Gut commensal bacteria enhance pathogenesis of a tumorigenic murine retrovirus

Spring, Jessica; Khan, Aly A.; Lara, Sophie; O'Grady, Kelly; Wilks, Jessica; Gurbuxani, Sandeep; Erickson, Steven A.; Fischbach, Michael; Jacobson, Amy N.; Chervonsky, Alexander V.; Golovkina, Tatyana V.

doi:10.1016/j.celrep.2022.111341

Cited by 6 publications

(8 citation statements)

References 87 publications

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“…In contrast to previous studies on spontaneous tumor development, including our study of leukemia induced by murine leukemia virus (MuLV) (6)(7)(8), the latency of hereditary lymphoma/sarcoma and mammary gland adenocarcinomas in Trp53 -/and Wnt1 transgenic mice, respectively, were unaffected by the absence of the microbiota (Figures 1A and 2A). These data suggest that unlike spontaneous malignancies, the development of cancer in gut distant organs arising from genetic predisposition may not be influenced by the microbiota.…”

Section: Discussioncontrasting

confidence: 99%

“…On the other hand, inborn mutations are inherited and can cause familial cancers (4,5). The influence of the microbiota on carcinogenesis stemming from spontaneous mutations has been well documented by us and other researchers (6)(7)(8). Furthermore, the development and progression of hereditary colorectal cancer, often caused by mutations in tumor suppressor genes such as Adenomatous polyposis coli (APC), has been found to be influenced by the microbiota (6,9).…”

Section: Introductionmentioning

confidence: 99%

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Microbiota may affect the tumor type but not overall tumor development in two models of heritable cancer

Spring,

Gurbuxani,

Golovkina

2023

Preprint

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Microbial impact on tumorigenesis of heritable cancers proximal to the gut is well documented. Whether the microbiota influences cancers arising from inborn mutations at sites distal to the gut is undetermined. Using two models of heritable cancer, we found the microbiota to be inconsequential for tumor development. However, the type of tumor that develops may be influenced by the microbiota. This work furthers our understanding of the microbial impact on tumor development.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Microbiota may affect the tumor type but not overall tumor development in two models of heritable cancer

Spring,

Gurbuxani,

Golovkina

2023

Preprint

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“…To characterize the effect of Phf6 loss further, we analyzed peripheral blood, splenic architecture, and bone marrow leukemic cell burden of primary recipient mice at 8 weeks after transplantation. Mice transplanted with cKO+Hoxa9 cells showed a higher frequency of GFP+ cells in peripheral blood at 8 Splenic infiltration was quantified using a previously described leukemia infiltration score (28) Ly6C+ population, also expressing CD11b, CD34, and CD16/32, but not Sca-1 (Fig. S4C).…”

Section: Phf6 Loss Increases Leukemic Disease Burdenmentioning

confidence: 99%

PHF6 suppresses self-renewal of leukemic stem cells in AML

Jalnapurkar,

Pawar,

George

et al. 2024

Preprint

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Acute myeloid leukemia is characterized by the uncontrolled proliferation of self-renewing myeloid progenitors. PHF6 is a chromatin-binding protein mutated in myeloid leukemias, and its loss increases mouse HSC self-renewal without malignant transformation. We report here that Phf6 knockout increases the aggressiveness of Hoxa9-driven AML over serial transplantation, and increases the frequency of leukemia initiating cells. We define the in vivo hierarchy of Hoxa9-driven AML and identify a population that we term the LIC-e (leukemia initiating cells enriched) population. We find that Phf6 loss has context-specific transcriptional effects, skewing the LIC-e transcriptome to a more stem-like state. We demonstrate that LIC-e accumulation in Phf6 knockout AML occurs not due to effects on cell cycle or apoptosis, but due to an increase in the fraction of its progeny that retain LIC-e identity. Overall, our work indicates that Phf6 loss increases AML self-renewal through context-specific effects on leukemia stem cells.

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“…While the effect of commensal microbe-derived metabolites on cellular activities and pathogen infections is clear, a reciprocal impact of the commensal microbiota and viral pathogens on metabolites has yet to be investigated. We previously showed commensal bacteria Lactobacillus murinus promotes the pathogenesis of murine retrovirus Murine Leukemia Virus (MuLV) (19). We used a similar model coupled with an unbiased metabolomics approach to investigate the influence of cross-talk between commensal bacteria and viral infection on metabolites.…”

Section: Introductionmentioning

confidence: 99%

Retroviral infection and commensal bacteria dependently alter the metabolomic profile in a sterile organ

Spring

Beilinson

DeFelice

et al. 2023

Preprint

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Both viruses and bacteria produce pathogen associated molecular patterns that may affect microbial pathogenesis and anti-microbial responses. Additionally, bacteria produce metabolites while viruses could change metabolic profiles of the infected cells. Here, we used an unbiased metabolomics approach to profile metabolites in spleens and blood of Murine Leukemia Virus-infected mice monocolonized with Lactobacillus murinus to show that viral infection significantly changes the metabolite profile of monocolonized mice. We hypothesize that these changes could contribute to viral pathogenesis or to the host response against the virus and thus, open a new avenue for future investigations.

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Gut commensal bacteria enhance pathogenesis of a tumorigenic murine retrovirus

Cited by 6 publications

References 87 publications

Microbiota may affect the tumor type but not overall tumor development in two models of heritable cancer

Microbiota may affect the tumor type but not overall tumor development in two models of heritable cancer

PHF6 suppresses self-renewal of leukemic stem cells in AML

Retroviral infection and commensal bacteria dependently alter the metabolomic profile in a sterile organ

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