IL1RAP antibodies block IL-1-induced expansion of candidate CML stem cells and mediate cell killing in xenograft models
Open accessAbstract
Chronic myeloid leukemia (CML) is currently treated with tyrosine kinase inhibitors, but these do not effectively eliminate the CML stem cells. As a consequence, CML stem cells persist and cause relapse in most patients upon drug discontinuation. Furthermore, no effective therapy exists for the advanced stages of the disease. Interleukin-1 receptor accessory protein (IL1RAP; IL1R3) is a coreceptor of interleukin-1 receptor type 1 and has been found upregulated on CML stem cells. Here, we show that primitive (CD34 + CD38 - ) CML cells, in contrast to corresponding normal cells, express a functional interleukin-1 (IL-1) receptor complex and respond with NF-κB activation and marked proliferation in response to IL-1. IL1RAP antibodies that inhibit IL-1 signaling could block these effects. In vivo administration of IL1RAP antibodies in mice transplanted with chronic and blast phase CML cells resulted in therapeutic effects mediated by murine effector cells. These results provide novel insights into the role of IL1RAP in CML and a strong rationale for the development of an IL1RAP antibody therapy to target residual CML stem cells.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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).”
From PU.1 enforces quiescence and limits hematopoietic stem cell expansion during inflammatory stress (2021) · cites this paper as Ågerstam et al., 2016
Cites
ROWLEY, J. D. (1973) · Nature · doi:10.1038/243290a0 · Cited by 4,291 · see citing works
Immunological and inflammatory functions of the interleukin-1 family
Dinarello, C. A. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132612 · Cited by 3,466 · see citing works
Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML
Jamieson, C. H. M., Ailles, L. E., Dylla, S. J., Muijtjens, M., Jones, C., Zehnder, J. L., Gotlib, J., Li, K., Manz, M. G., Keating, A., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040258 · Cited by 1,485 · see citing works
Chu, S., McDonald, T., Lin, A., Chakraborty, S., Huang, Q., Snyder, D. S., & Bhatia, R. (2011) · Blood · doi:10.1182/blood-2010-12-327437 · Cited by 245 · see citing works
Dipeptidylpeptidase IV (CD26) defines leukemic stem cells (LSC) in chronic myeloid leukemia
Herrmann, H., Sadovnik, I., Cerny-Reiterer, S., Rülicke, T., Stefanzl, G., Willmann, M., Hoermann, G., Bilban, M., Blatt, K., Herndlhofer, S., et al. (2014) · Blood · doi:10.1182/blood-2013-10-536078 · Cited by 223 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Cancer stem cells—Origins and biomarkers: Perspectives for targeted personalized therapies
Walcher, L., Kistenmacher, A.-K., Suo, H., Kitte, R., Dluczek, S., Strauß, A., Blaudszun, A.-R., Yevsa, T., Fricke, S., & Kossatz-Boehlert, U. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01280 · Cited by 1,007 · see citing works
Carey, A., Edwards, D. K., Eide, C. A., Newell, L., Traer, E., Medeiros, B. C., Pollyea, D. A., Deininger, M. W., Collins, R. H., Tyner, J. W., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.03.018 · Cited by 270 · see citing works
PU.1 enforces quiescence and limits hematopoietic stem cell expansion during inflammatory stress
Chavez, J. S., Rabe, J. L., Loeffler, D., Higa, K. C., Hernandez, G., Mills, T. S., Ahmed, N., Gessner, R. L., Ke, Z., Idler, B. M., et al. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20201169 · Cited by 91 · see citing works
“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…”
BackgroundKinstrie, R., Horne, G. A., Morrison, H., Irvine, D., Munje, C., Castañeda, E. G., Moka, H. A., Dunn, K., Cassels, J. E., Parry, N., et al. (2020) · Leukemia · doi:10.1038/s41375-019-0684-5 · Cited by 67 · see citing works
- Authors
- Ågerstam, H., Hansen, N., von Palffy, S., Sandén, C., Reckzeh, K., Karlsson, C., Lilljebjörn, H., Landberg, N., Askmyr, M., Högberg, C., Rissler, M., Porkka, K., Wadenvik, H., Mustjoki, S., Richter, J., Järås, M., & Fioretos, T.
- Affiliations
- Lund University (SE)
- Department of Clinical Genetics, Lund University, Lund, Sweden;
- University of Helsinki (FI)
- University of Gothenburg (SE)
- Skåne University Hospital (SE)
- Corresponding author
- Ågerstam, Helena
- Hansen, Nils
- Järås, Marcus
- Fioretos, Thoas
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2016-12-08
- Volume
- 128
- Issue
- 23
- Pages
- 2683-2693
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2519273869
- Cited by
- 98
- References
- 5
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 10 · 2023: 11 · 2022: 10 · 2021: 15 · 2020: 10 · 2019: 12 · 2018: 5 · 2017: 13 · 2016: 2
- FWCI
- 10.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Blood (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Chronic Myeloid Leukemia Treatments
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- interleukin-1 receptor, chronic myeloid leukemia, IL-1 signaling, NF-κB activation, xenograft models, antibody therapy, cell killing
- MeSH terms
- Animals, Antibodies, Neoplasm, Female, Humans, Interleukin-1, Male, Neoplasm Proteins, Neoplastic Stem Cells, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Mice, Knockout, Xenograft Model Antitumor Assays, Mice, Interleukin-1 Receptor Accessory Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
