Evidence map›Paper›PMID 41535568›Full record

ArticleLeukemia2026

Unravelling co-mutational patterns with prognostic implications in NPM1 mutated adult acute myeloid leukemia - a HARMONY study.

Alberto Hernández-Sánchez, Ángela Villaverde Ramiro, Eric Sträng, Amin T Turki, María Abáigar, Jurjen Versluis, Ian Thomas, Marta Sobas, Javier Martínez Elicegui, Gastone Castellani and 23 more

Abstract read
In one paragraph

Article in Leukemia, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
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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

33 authors.

Alberto Hernández-SánchezHematology Department, University Hospital of Salamanca, Salamanca, Spain.ORCID 0000-0002-6601-3096
Ángela Villaverde RamiroInstitute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.ORCID 0000-0002-7337-7218
Eric SträngCharité Universitätsmedizin Berlin, Berlin, Germany.
Amin T TurkiMarienhospital University Hospital, Ruhr-University Bochum, Bochum, Germany.ORCID 0000-0003-1347-3360
María AbáigarInstitute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
Jurjen VersluisErasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.ORCID 0000-0003-2372-1663
Ian ThomasCentre for Trials Research, Cardiff University, Cardiff, UK.
Marta SobasDepartment of Hematology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, Poland.
Javier Martínez EliceguiInstitute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.ORCID 0000-0001-5294-6162
Gastone CastellaniDepartment of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.ORCID 0000-0003-4892-925X
Axel BennerDivision of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Raúl AzibeiroHematology Department, University Hospital of Salamanca, Salamanca, Spain.ORCID 0000-0002-3382-3674
Jesse M TetteroDepartment of Hematology, Amsterdam UMC location VUMC, Amsterdam, Netherlands.ORCID 0000-0002-0811-0824
Rabea MecklenbrauckDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.ORCID 0009-0005-9374-300X
Joaquín Martínez-LópezHospital Universitario 12 de Octubre, Madrid, Spain.ORCID 0000-0001-7908-0063
Marta PratcoronaHematology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Ken I MillsPatrick G Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK.ORCID 0000-0002-6362-4481
Guillermo SanzCIBERONC, Instituto de Salud Carlos III, Madrid, Spain.ORCID 0000-0002-2767-8191
Maria Teresa VosoUniversity of Rome Tor Vergata, Rome, Italy.ORCID 0000-0002-6164-4761
Lehmann SörenUppsala University Hospital, Uppsala, Sweden.
Christoph RölligMedical Dept. I, University Hospital TU Dresden, Dresden, Germany.ORCID 0000-0002-3791-0548
Christian ThiedeMedical Dept. I, University Hospital TU Dresden, Dresden, Germany.ORCID 0000-0003-1241-2048
Klaus H MetzelerUniversity of Leipzig, Leipzig, Germany.ORCID 0000-0003-3920-7490
Konstanze DöhnerDepartment of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.ORCID 0000-0002-2261-9862
Michael HeuserDepartment of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.ORCID 0000-0001-5318-9044
Torsten HaferlachMLL Munich Leukemia Laboratory, Munich, Germany.ORCID 0000-0003-0196-2837
Peter Jm ValkErasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.ORCID 0000-0002-8857-9461
Nigel RussellGuy's and St Thomas' Hospital, London, UK.
Jesús María Hernández-RivasHematology Department, University Hospital of Salamanca, Salamanca, Spain.ORCID 0000-0002-9661-9371
Brian HuntlyWellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK.ORCID 0000-0003-0312-161X
Gert OssenkoppeleDepartment of Hematology, Amsterdam UMC location VUMC, Amsterdam, Netherlands.
Hartmut DöhnerDepartment of Internal Medicine III, University Hospital of Ulm, Ulm, Germany.ORCID 0000-0003-2116-5536
Lars BullingerDepartment of Hematology, Oncology, and Tumor Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany. lars.bullinger@charite.de.ORCID 0000-0002-5890-5510

Funding

Deutsche Forschungsgemeinschaft (German Research Foundation) FU 356/12-1Deutsche Krebshilfe (German Cancer Aid) 70115737Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III) CM23/00101
6 · The paper itself

Abstract

NPM1-mutated (NPM1-mut) acute myeloid leukemia (AML) is generally associated with a more favorable outcome, although the presence of additional gene mutations can influence patient prognosis. We analyzed intensively-treated adult NPM1-mut AML patients included in the HARMONY Alliance database. A newly developed risk classification, which included combinations of co-mutations in FLT3-ITD, DNMT3A, IDH1/IDH2, and TET2 genes, was applied to a training cohort of NPM1-mut AML patients included in clinical trials (n = 1001), an internal validation cohort more representative of real-world settings (n = 762), and an external validation cohort enrolled in UK-NCRI trials (n = 585). The HARMONY classification considered 51.8% of the NPM1-mut AML training cohort patients as favorable, 24.8% as intermediate, and 23.4% as adverse risk, with median overall survival (OS) of 14.4, 2.2, and 0.9 years, respectively; p < 0.001), thereby reclassifying 42.7% of NPM1-mut patients into a different European LeukemiaNet (ELN) 2022 risk category. These results were confirmed both in an internal and external validation cohort. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) showed the highest benefit in the NPM1-mut adverse-risk subgroup. The HARMONY classification provides the basis for a refined genetic risk stratification for adult NPM1-mut AML with potential clinical impact on allo-HSCT decision-making.

Indexed as

Biomarkers, TumorLeukemia, Myeloid, AcuteMutationNuclear ProteinsAdultAgedDioxygenasesDNA-Binding ProteinsDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3AFemalefms-Like Tyrosine Kinase 3HumansIsocitrate DehydrogenaseMaleMiddle AgedBiomarkers, TumorDioxygenasesDNA-Binding ProteinsDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNMT3A protein, humanFLT3 protein, humanfms-Like Tyrosine Kinase 3IDH1 protein, humanIDH2 protein, humanIsocitrate DehydrogenaseNPM1 protein, humanNuclear ProteinsNucleophosminProto-Oncogene ProteinsTET2 protein, human

Identifiers

PMID41535568
PMCPMC12875867

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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.