Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder
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Mammalian microRNAs are emerging as key regulators of the development and function of the immune system. Here, we report a strong but transient induction of miR-155 in mouse bone marrow after injection of bacterial lipopolysaccharide (LPS) correlated with granulocyte/monocyte (GM) expansion. Demonstrating the sufficiency of miR-155 to drive GM expansion, enforced expression in mouse bone marrow cells caused GM proliferation in a manner reminiscent of LPS treatment. However, the miR-155–induced GM populations displayed pathological features characteristic of myeloid neoplasia. Of possible relevance to human disease, miR-155 was found to be overexpressed in the bone marrow of patients with certain subtypes of acute myeloid leukemia (AML). Furthermore, miR-155 repressed a subset of genes implicated in hematopoietic development and disease. These data implicate miR-155 as a contributor to physiological GM expansion during inflammation and to certain pathological features associated with AML, emphasizing the importance of proper miR-155 regulation in developing myeloid cells during times of inflammatory stress.
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Mice overexpressing miR-155 develop chronic-inflammatory states and hematopoietic malignancies.
“mice overexpressing miR-155 develop chronic-inflammatory states and hematopoietic malignancies [23].”
From Microglia specific deletion of miR-155 in Alzheimer’s disease mouse models reduces amyloid-β pathology but causes hyperexcitability and seizures (2023) · cites this paper as [23]
The Results and Discussion report abnormal myeloid proliferation in mice with sustained miR-155 expression, including a myeloproliferative disorder with preleukemic features. The Discussion does not report that these mice developed chronic inflammation or frank hematopoietic malignancy; it explicitly says no frank myeloid leukemia was observed within two months. Page numbers are not available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredmiR-155 drives cell differentiation.
“In addition to its function in immunity, miR-155 drives cell differentiation [59].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [59]
The Results report that enforced miR-155 expression in hematopoietic stem cells increased granulocyte/monocyte cells while reducing B cells and erythroid precursors. The Discussion links miR-155 to hematopoietic development but suggests that sustained expression may prevent those myeloid cells from completing their developmental programs. Thus the paper supports an effect on cell development, not the unqualified claim that miR-155 drives cell differentiation. (LLM, conf=0.83)
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Cites
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Requirement of <i>bic/microRNA-155</i> for Normal Immune Function
Rodriguez, A., Vigorito, E., Clare, S., Warren, M. V., Couttet, P., Soond, D. R., van Dongen, S., Grocock, R. J., Das, P. P., Miska, E. A., et al. (2007) · Science · doi:10.1126/science.1139253 · Cited by 1,833 · see citing works
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- Authors
- O'Connell, R. M., Rao, D. S., Chaudhuri, A. A., Boldin, M. P., Taganov, K. D., Nicoll, J., Paquette, R. L., & Baltimore, D.
- Affiliations
- 1Department of Biology, California Institute of Technology, Pasadena, CA 91125
- California Institute of Technology (US)
- University of California, Los Angeles (US)
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2008-02-25
- Volume
- 205
- Issue
- 3
- Pages
- 585-594
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2275382
- OpenAlex
- W2160098916
- Cited by
- 681
- References
- 5
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 16 · 2023: 10 · 2022: 15 · 2021: 17 · 2020: 18 · 2019: 25 · 2018: 20 · 2017: 42 · 2016: 38 · 2015: 45 · 2014: 56 · 2013: 83 · 2012: 68
- FWCI
- 24.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-sa)
- Funders
- Howard Hughes Medical Institute
- Cancer Research Institute
- American Society of Hematology
- California Institute of Technology
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- miR-155, hematopoietic stem cells, myeloproliferative neoplasms, lipopolysaccharide, inflammation, acute myeloid leukemia, bone marrow, myeloid neoplasms, gene repression, hematopoietic development
- MeSH terms
- Animals, Female, Granulocytes, Hematopoiesis, Hematopoietic Stem Cells, Humans, Immunity, Innate, Lipopolysaccharides, Mice, Inbred C57BL, Monocytes, Myeloproliferative Disorders, Leukemia, Myeloid, Acute, Gene Expression, 3' Untranslated Regions, MicroRNAs, Mice
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