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CD47 Is an Adverse Prognostic Factor and Therapeutic Antibody Target on Human Acute Myeloid Leukemia Stem Cells
Open accessAbstract
Acute myeloid leukemia (AML) is organized as a cellular hierarchy initiated and maintained by a subset of self-renewing leukemia stem cells (LSC). We hypothesized that increased CD47 expression on human AML LSC contributes to pathogenesis by inhibiting their phagocytosis through the interaction of CD47 with an inhibitory receptor on phagocytes. We found that CD47 was more highly expressed on AML LSC than their normal counterparts, and that increased CD47 expression predicted worse overall survival in three independent cohorts of adult AML patients. Furthermore, blocking monoclonal antibodies directed against CD47 preferentially enabled phagocytosis of AML LSC and inhibited their engraftment in vivo. Finally, treatment of human AML LSC-engrafted mice with anti-CD47 antibody depleted AML and targeted AML LSC. In summary, increased CD47 expression is an independent, poor prognostic factor that can be targeted on human AML stem cells with blocking monoclonal antibodies capable of enabling phagocytosis of LSC.
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“increased CD47 levels on the surface of malignant cells correlate with dismal prognosis in subjects with AML, esophageal carcinoma, and ovarian cancer [888–891].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [891]
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Metadata
- Authors
- Majeti, R., Chao, M. P., Alizadeh, A. A., Pang, W. W., Jaiswal, S., Gibbs, K. D., van Rooijen, N., & Weissman, I. L.
- Affiliations
- Stanford Medicine (US)
- Institute for Stem Cell Biology and Regenerative Medicine (US)
- Stanford University (US)
- Corresponding author
- Majeti, Ravindra
- Weissman, Irving L.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2009-07
- Volume
- 138
- Issue
- 2
- Pages
- 286-299
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC2726837
- OpenAlex
- W2097126393
- Cited by
- 1,752
- References
- 47
- Citations by year
- 2026: 73 · 2025: 143 · 2024: 149 · 2023: 183 · 2022: 147 · 2021: 163 · 2020: 142 · 2019: 106 · 2018: 86 · 2017: 108 · 2016: 78 · 2015: 85 · 2014: 61 · 2013: 65 · 2012: 67
- FWCI
- 22.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1477 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Cancer Institute (R01 CA86017, R01CA086017, T32CA009302)
- National Institute of Allergy and Infectious Diseases (T32AI007290)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Pharmacology (medical) › Flavonoids in Medical Research
- Keywords
- CD47, acute myeloid leukemia, leukemia stem cells, prognostic factors, anti-CD47 monoclonal antibody, phagocytosis, overall survival, engraftment, targeted therapy
- MeSH terms
- Animals, Antibodies, Monoclonal, Humans, Phagocytosis, Prognosis, Receptors, Immunologic, Leukemia, Myeloid, Acute, Mice, CD47 Antigen
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