Cited by 127Acute Myeloid Leukemia ResearchMonoclonal and Polyclonal Antibodies ResearchChronic Myeloid Leukemia Treatments

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

Selective killing of candidate AML stem cells by antibody targeting of IL1RAP

Abstract

IL1RAP, a co-receptor for interleukin (IL)-1 and IL-33 receptors, was previously found to be highly upregulated on candidate chronic myeloid leukemia stem cells, allowing for leukemia-selective killing using IL1RAP-targeting antibodies. We analyzed IL1RAP expression in a consecutive series of 29 patients with acute myeloid leukemia (AML) and, based on the level of expression in mononuclear cells (MNCs), we divided the samples into 3 groups: IL1RAP low (n = 6), IL1RAP intermediate (n = 11), and IL1RAP high (n = 12). Within the CD34+CD38- population, the intermediate and high groups expressed higher levels of IL1RAP than did corresponding normal cells. With the aim to target AML stem cells, an anti-IL1RAP monoclonal antibody was generated followed by isotype switching for improved antibody-dependent, cell-mediated cytotoxicity activity. Using this antibody, we achieved selective killing of AML MNC, CD34+CD38+, and CD34+CD38- cells. Our findings demonstrate that IL1RAP is a promising new therapeutic target in AML.

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Crossref · 10.1182/blood-2012-09-458935

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2 of 2 references verified0 citation errors · 0 not checkable

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  • Aberrant signaling via IL-1 and the downstream IRAK/TRAF pathway shared by IL-1R and TLRs has been implicated as a driver of survival and/or expansion of MDS and myeloid leukemia stem cells.

    “Aberrant signaling via IL-1 and the downstream IL-1 receptor associated kinase/TNF receptor associated factor pathway shared by IL-1R and TLRs has been implicated as a driver of survival and/or expansion of MDS and myeloid leukemia stem cells (Ågerstam et al., 2016; Askmyr et al., 2013; Barreyro et al., 2012; Carey et al., 2017; Muto et al., 2020; Smith et al., 2019; Zhang et al., 2016).”

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Research works printed but not linked: 9

  1. Dinarello, 2012, Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases., Nat Rev Drug Discov, 11, 633, 10.1038/nrd3800 · DOI
  2. Järås, 2010, Isolation and killing of candidate chronic myeloid leukemia stem cells by antibody targeting of IL-1 receptor accessory protein., Proc Natl Acad Sci USA, 107, 16280, 10.1073/pnas.1004408107 · DOI
  3. Barreyro, 2012, Overexpression of IL-1 receptor accessory protein in stem and progenitor cells and outcome correlation in AML and MDS., Blood, 120, 1290, 10.1182/blood-2012-01-404699 · DOI · Paper page
  4. Estrov, 1992, Inhibition of acute myelogenous leukemia blast proliferation by interleukin-1 (IL-1) receptor antagonist and soluble IL-1 receptors., Blood, 79, 1938, 10.1182/blood.V79.8.1938.1938 · DOI
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  6. Bonnet, 1997, Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell., Nat Med, 3, 730, 10.1038/nm0797-730 · DOI
  7. Taussig, 2008, Anti-CD38 antibody-mediated clearance of human repopulating cells masks the heterogeneity of leukemia-initiating cells., Blood, 112, 568, 10.1182/blood-2007-10-118331 · DOI · Paper page
  8. Sarry, 2011, Human acute myelogenous leukemia stem cells are rare and heterogeneous when assayed in NOD/SCID/IL2Rγc-deficient mice., J Clin Invest, 121, 384, 10.1172/JCI41495 · DOI
  9. Eppert, 2011, Stem cell gene expression programs influence clinical outcome in human leukemia., Nat Med, 17, 1086, 10.1038/nm.2415 · DOI

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Metadata

Authors
Askmyr, M., Ågerstam, H., Hansen, N., Gordon, S., Arvanitakis, A., Rissler, M., Juliusson, G., Richter, J., Järås, M., & Fioretos, T.
Affiliations
Lund University (SE)
Venue
Blood
Published
2013-05-02
Volume
121
Issue
18
Pages
3709-3713
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
OpenAlex
W2074711837
Cited by
127
References
2
Citations by year
2026: 3 · 2025: 11 · 2024: 9 · 2023: 10 · 2022: 16 · 2021: 15 · 2020: 10 · 2019: 7 · 2018: 8 · 2017: 13 · 2016: 5 · 2015: 10 · 2014: 6 · 2013: 3
FWCI
5.74
Type
journal article
Language
en
Open access
closed
Locations
  • Blood (publishedVersion)
  • PubMed (publishedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
  • Health Sciences › Medicine › Hematology › Chronic Myeloid Leukemia Treatments
Keywords
IL1RAP, acute myeloid leukemia, leukemia stem cells, antibody targeting, IL-33 receptor, monoclonal antibodies, antibody-dependent cellular cytotoxicity, CD34+CD38- cells, therapeutic target, selective killing
MeSH terms
Adult, Aged, Aged, 80 and over, Antibodies, Antibody Specificity, Cells, Cultured, Cytotoxicity, Immunologic, Female, Humans, Immunotherapy, Male, Middle Aged, Neoplastic Stem Cells, Leukemia, Myeloid, Acute, Interleukin-1 Receptor Accessory Protein, Molecular Targeted Therapy

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