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IL-6 Controls Leukemic Multipotent Progenitor Cell Fate and Contributes to Chronic Myelogenous Leukemia Development
Open accessAbstract
Using a mouse model recapitulating the main features of human chronic myelogenous leukemia (CML), we uncover the hierarchy of leukemic stem and progenitor cells contributing to disease pathogenesis. We refine the characterization of CML leukemic stem cells (LSCs) to the most immature long-term hematopoietic stem cells (LT-HSCs) and identify some important molecular deregulations underlying their aberrant behavior. We find that CML multipotent progenitors (MPPs) exhibit an aberrant B-lymphoid potential but are redirected toward the myeloid lineage by the action of the proinflammatory cytokine IL-6. We show that BCR/ABL activity controls Il-6 expression thereby establishing a paracrine feedback loop that sustains CML development. These results describe how proinflammatory tumor environment affects leukemic progenitor cell fate and contributes to CML pathogenesis.
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“In particular, the SASP-associated cytokines TNF, IFN, and IL-6 all play significant roles in the pathogenesis of myeloproliferative neoplasms (MPNs), 52 MDSs, 53 and acute myeloid leukemia (AML).54”
From Inflammatory bone marrow microenvironment (2019) · cites this paper as [52]
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Metadata
- Authors
- Reynaud, D., Pietras, E., Barry-Holson, K., Mir, A., Binnewies, M., Jeanne, M., Sala-Torra, O., Radich, J. P., & Passegué, E.
- Affiliations
- University of California, San Francisco (US)
- Standard BioTools (United States) (US)
- Fred Hutch Cancer Center (US)
- Corresponding author
- Reynaud, Damien
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 20
- Issue
- 5
- Pages
- 661-673
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC3220886
- OpenAlex
- W1974815398
- Cited by
- 335
- References
- 34
- Citations by year
- 2026: 10 · 2025: 22 · 2024: 17 · 2023: 26 · 2022: 26 · 2021: 33 · 2020: 27 · 2019: 23 · 2018: 19 · 2017: 25 · 2016: 20 · 2015: 28 · 2014: 24 · 2013: 19 · 2012: 16
- FWCI
- 12.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- University of California, San Francisco
- National Heart, Lung, and Blood Institute (HL092471, R01HL092471)
- Topics
- Health Sciences › Medicine › Hematology › Chronic Myeloid Leukemia Treatments
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- interleukin-6, chronic myeloid leukemia, multipotent progenitors, leukemia stem cells, long-term hematopoietic stem cells, BCR-ABL, myeloid differentiation, paracrine signaling, cell fate specification
- MeSH terms
- Animals, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Interleukin-6, Fusion Proteins, bcr-abl, Feedback, Physiological, Multipotent Stem Cells, Mice, Precursor Cells, B-Lymphoid
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