Cited by 335Chronic Myeloid Leukemia TreatmentsAcute Myeloid Leukemia ResearchHematopoietic Stem Cell Transplantation

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IL-6 Controls Leukemic Multipotent Progenitor Cell Fate and Contributes to Chronic Myelogenous Leukemia Development

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Reynaud, Damien, Pietras, Eric, Barry-Holson, Keegan, Mir, Alain, Binnewies, Mikhail, Jeanne, Marion, Sala-Torra, Olga, Radich, Jerald P., Passegué, Emmanuelle·2011·Cancer Cell

DOI 10.1016/j.ccr.2011.10.012PMC PMC3220886

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Abstract

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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Impaired immune and acute-phase responses in interleukin-6-deficient mice
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“IL-6 Contributes to CML Development To confirm the function of IL-6 in CML pathogenesis, we evaluated disease progression in the absence of IL-6 signaling by crossing BA mice with Il-6 / mice (Kopf et al., 1994).”
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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
ORCID: Reynaud, Damien
Pietras, Eric
Binnewies, Mikhail
Jeanne, Marion
Radich, Jerald P.
Venue: Cancer Cell
Publisher: Elsevier BV
Published: 2011-11
Volume: 20
Issue: 5
Pages: 661-673
ISSN: 1535-6108 (ISSN-L)
DOI: 10.1016/j.ccr.2011.10.012
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 624 d)
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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IL-6 Controls Leukemic Multipotent Progenitor Cell Fate and Contributes to Chronic Myelogenous Leukemia Development

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