Cited by 1,752Phagocytosis and Immune RegulationAcute Myeloid Leukemia ResearchFlavonoids in Medical Research

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CD47 Is an Adverse Prognostic Factor and Therapeutic Antibody Target on Human Acute Myeloid Leukemia Stem Cells

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Majeti, Ravindra, Chao, Mark P., Alizadeh, Ash A., Pang, Wendy W., Jaiswal, Siddhartha, Gibbs, Kenneth D., van Rooijen, Nico, Weissman, Irving L.·2009·Cell

DOI 10.1016/j.cell.2009.05.045PMC PMC2726837

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Abstract

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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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: Majeti, Ravindra
Chao, Mark P.
Alizadeh, Ash A.
Pang, Wendy W.
Jaiswal, Siddhartha
Gibbs, Kenneth D.
Weissman, Irving L.
Venue: Cell
Publisher: Elsevier BV
Published: 2009-07
Volume: 138
Issue: 2
Pages: 286-299
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2009.05.045
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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CD47 Is an Adverse Prognostic Factor and Therapeutic Antibody Target on Human Acute Myeloid Leukemia Stem Cells

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