Evidence map›Paper›PMID 40229904›Full record

ArticleBiomarker research2025

IL1RAP is an immunotherapeutic target for normal karyotype triple-mutated acute myeloid leukemia.

Arnaud Métois, Marie-Eve Bordeleau, Louis Theret, Azadeh Hajmirza, Ossama Moujaber, Jean-François Spinella, Jalila Chagraoui, Nadine Mayotte, Isabel Boivin, Éric Audemard and 20 more

Abstract read
In one paragraph

Article in Biomarker research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
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  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

30 authors.

Arnaud MétoisThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Marie-Eve BordeleauThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Louis TheretThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Azadeh HajmirzaThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Ossama MoujaberThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Jean-François SpinellaThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Jalila ChagraouiThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Nadine MayotteThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Isabel BoivinThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Éric AudemardThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Léo AubertThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Véronique LisiThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Banafsheh KhakipoorThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Azer FarahThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Éric BonneilThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Alma RobertMedical Devices Research Center, National Research Council Canada, Montréal, Québec, H4P 2R2, Canada.
Julie LippensMedical Devices Research Center, National Research Council Canada, Montréal, Québec, H4P 2R2, Canada.
Anna MoraitisMedical Devices Research Center, National Research Council Canada, Montréal, Québec, H4P 2R2, Canada.
François BéliveauThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Albert FeghalyThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Geneviève BoucherThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Richard MarcotteHuman Health Therapeutic Research Center National Research Council Canada, Montréal, Québec, H4P 2R2, Canada.
Patrick GendronThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Pierre ThibaultThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Sébastien LemieuxThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Guillaume Richard-CarpentierThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Vincent-Philippe LavalléeThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Josée HébertThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Philippe P RouxThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada.
Guy SauvageauThe Leucegene Project at Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Québec, H3 T 1 J4, Canada. guy.sauvageau@umontreal.ca.

Funding

Genome Canada 4524Génome Québec,Canada 13528Stem Cell Network HZN-C4R1-1
6 · The paper itself

Abstract

backgroundSurface antigens of potential clinical significance remain under-characterized in AML. The European Leukemia Network classifies normal karyotype AML (NK-AML) mutated for NPM1 (NPM1c) as a distinct entity associated with favorable outcomes if not associated with FLT3-ITD mutation. A subset of NPM1c NK-AML shows additional mutations in 2 genes: FLT3 (FLT3-ITD) and DNMT3 A. These leukemias, also referred to as NK triple mutated AML (NKt-AML), are particularly difficult to eradicate with current treatment options. Therefore, novel therapies are necessary that use proteins specifically expressed at the surface.

methodsIn order to identify surface antigens for immunotherapy in NKt-AML, an extensive multi-omic analysis was conducted on primary AML samples. Surface proteome enrichment was performed on 100 primary AML samples, twelve of which were NKt-AML. Transcriptome analysis was carried out on the 691 primary AML samples, and single-cell RNA sequencing was conducted on 23 primary AML samples.

resultsHerein, using multi-omics data from the Leucegene collection, we identify IL1RAP as a promising antigen for this AML subgroup. We demonstrate that IL1RAP is expressed at the surface of primitive AML cells reminiscent of leukemic stem cells in NKt-AML primary human AML specimens, while showing relatively low expression levels in normal bone marrow HSCs. Furthermore, results indicate that elevated IL1RAP expression associates with poor overall and relapse-free survival in the Leucegene cohort of AML patients and predicts nonresponse to hematopoietic stem cell transplantation. Finally, we show that IL1RAP protein is internalized following exposure to specific antibodies, suggesting that IL1RAP represents an interesting target for antibody-drug conjugate development in NKt-AML.

conclusionsIL1RAP exhibits preferential expression within NKt-AML, correlating with diminished overall survival rates and diminished responsiveness to hematopoietic stem cell transplantation. Moreover, internalization of IL1RAP presents a promising avenue for immunotherapeutic intervention.

Indexed as

Acute myeloid leukemiaCancerIL1RAPImmunotherapySingle cellSurfaceome

Identifiers

PMID40229904
PMCPMC11995633

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.