ArticleNature cancer2026
Integrated proteogenomic and metabolomic profiling of acute myeloid leukemias to identify molecular subtypes and associated therapy targets.
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In one paragraph
Article in Nature cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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.
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.
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Who cites it
2 citing papers in PubMed.
- Two Decades ofCancers · 2026Review
- Assessing current capabilities for incorporating lipidomics in multiomics data integration.Briefings in bioinformatics · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
68 authors.
Shih-Chun A Chu *Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
Yi Hsiao *Gilbert S. Omenn Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-9435-0305
Chenwei Wang *Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0002-0920-8639
Jennifer E Kyle *Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Raghav JainBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.ORCID http://orcid.org/0000-0002-1284-6762
Yamei DengGilbert S. Omenn Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-3680-5930
Marina A GritsenkoEnvironmental and Molecular Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.ORCID http://orcid.org/0000-0001-9992-9829
Leanne E HenryDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.
Jonathan T LeiLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
Yongchao DouLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
Bahar TercanInstitute for Systems Biology, Seattle, WA, USA.
Zhiao ShiLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
Mahnoor N GondalGilbert S. Omenn Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-9419-6758
Chia-Feng TsaiBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.ORCID http://orcid.org/0000-0002-6514-6911
John M ElizarrarasTexas Children's Hospital, Department of Pediatrics, Houston, TX, USA.ORCID http://orcid.org/0000-0001-7759-2540
Rosalie K ChuEnvironmental and Molecular Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Fengchao YuDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-7695-3698
Sunil K JoshiDepartment of Medicine, Divisions of Hematology and Oncology, Stanford University School of Medicine, Stanford, CA, USA.
Xiaojun JingDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.
Daniel A PolaskyDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-0515-1735
Karl K WeitzBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Ginny Xiaohe LiDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.
Vanessa L PaurusBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.ORCID http://orcid.org/0000-0002-8960-2926
Chaevien S ClendinenEnvironmental and Molecular Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.ORCID http://orcid.org/0000-0002-1487-4126
Athena A SchepmoesBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Priscila M LalliBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Josie G EderBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Javier E FloresBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.ORCID http://orcid.org/0000-0002-1550-1655
Kelly G StrattonBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
James C PinoBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Camilo PossoBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Vladislav A PetyukBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Tyler J SagendorfBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Yuanwei XuDepartment of Pathology. Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-7020-7961
Omar M IbrahimDepartment of Medicine, Washington University in St. Louis, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-9903-6657
Ronald J MooreBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.ORCID http://orcid.org/0000-0003-2806-2855
Rui ZhaoEnvironmental and Molecular Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Jin ChenDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.
Matthew E MonroeBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Mathangi ThiagarajanOffice of Cancer Clinical Proteomics Research, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD, USA.
Galen HostetterVan Andel Research Institute, Grand Rapids, MI, USA.
Chelsea NewtonVan Andel Research Institute, Grand Rapids, MI, USA.
Eunkyung AnOffice of Cancer Clinical Proteomics Research, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD, USA.ORCID http://orcid.org/0000-0003-3096-9413
Ana I RoblesOffice of Cancer Clinical Proteomics Research, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD, USA.ORCID http://orcid.org/0000-0001-5019-4374
Xu ZhangOffice of Cancer Clinical Proteomics Research, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD, USA.
Nathan J EdwardsDepartment of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, Washington DC, USA.
Yin LuICF, Rockville, MD, USA.
Hui ZhangDepartment of Pathology. Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-8726-7098
Haitham AbdelhakimUniversity of Kansas Medical Center, The University of Kansas Cancer Center, Kansas City, KS, USA.
Paul D PiehowskiEnvironmental and Molecular Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.ORCID http://orcid.org/0000-0001-5108-2227
Mehdi MesriOffice of Cancer Clinical Proteomics Research, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Rockville, MD, USA.
Richard D SmithBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Chandan Kumar-SinhaDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-8696-3400
Cristina E TognonKnight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
Jennifer DunlapKnight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
Elie TraerKnight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
Li DingDivision of Oncology, Department of Medicine, Washington University, St. Louis, MO, USA.ORCID http://orcid.org/0000-0003-1517-2975
Jeffrey W TynerDepartment of Cell, Developmental and Cancer Biology, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.ORCID http://orcid.org/0000-0002-2133-0960
Arul M ChinnaiyanDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0001-9282-3415
Gilbert S OmennGilbert S. Omenn Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-8976-6074
Karin D RodlandBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Saravana M DhanasekaranDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.
Sara J C GoslineBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA.
Alexey I NesvizhiskiiDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA. nesvi@med.umich.edu.ORCID http://orcid.org/0000-0002-2806-7819
Bing ZhangLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA. Bing.Zhang@bcm.edu.ORCID http://orcid.org/0000-0001-8676-2425
Tao LiuBiological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA. Tao.Liu@pnnl.gov.ORCID http://orcid.org/0000-0001-9529-6550
Marcin P CieslikDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA. mcieslik@med.umich.edu.ORCID http://orcid.org/0000-0002-5467-1040
Clinical Proteomic Tumor Analysis Consortium
Funding
Center for Advanced Multi-Omic Characterization of CancerU24CA271012 · NCI · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI Tao Liu · 2022 to 2026
$6.6MProteogenomic characterization of early and late resistance mechanisms in acute myeloid leukemiaU01CA271412 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI BRIAN J DRUKER, Paul D Piehowski · 2022 to 2026
$5.8MPNNL Proteome Characterization CenterU24CA210955 · NCI · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI LIU, TAO, SMITH, RICHARD D · 2016 to 2020
$5.3MProteogenomic translator for cancer biomarker discovery towards precision medicineU24CA271114 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Avi Ma'ayan, Pei Wang · 2022 to 2026
$5.0MDefining the stromal landscape that sustains AML drug resistanceF30CA239335 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI JOSHI, SUNIL KUMAR · 2019 to 2022
$187kNCI NIH HHS F30 CA239335NCI NIH HHS U01 CA271412NCI NIH HHS U24 CA210955NCI NIH HHS U24 CA271012NCI NIH HHS U24 CA271114
Abstract
Acute myeloid leukemia (AML) is a genetically and phenotypically heterogeneous hematological malignancy. Here, to better define this clinically taxing and translationally challenging malignancy, we applied a multiomics approach, consisting of 13 modalities to analyze 173 treatment-naive individuals with AML. By integrating these 'omes', we identified distinct AML subtypes, genotype-phenotype associations, biomarkers and pathobiological mechanisms. Across the spectrum of primitive and committed AML, we found extensive metabolomic and lipidomic reprogramming driven by divergent MYC and mTOR activity. We linked metabolic changes to striking hyperacetylation of mitochondrial proteins in CEBPA-mutant AML. Protein-centric subtyping revealed a distinct NPM1-mutant subset characterized by outlier expression of FOXC1 and HOXB8/9. To nominate therapeutic targets across subtypes, we developed a multiomic machine-learning approach and validated MTA1 as a contributor to panobinostat resistance. Altogether our findings underscore the complex nature of AML and provide a clinically and translationally informed unified view that reveals coalescent phenotypes across multiomic layers.
Indexed as
Leukemia, Myeloid, AcuteMetabolomicsProteogenomicsBiomarkers, TumorCCAAT-Enhancer-Binding ProteinsHumansMolecular Targeted TherapyMultiomicsMutationNucleophosminBiomarkers, TumorCCAAT-Enhancer-Binding ProteinsCEBPA protein, humanNPM1 protein, humanNucleophosmin
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