Language
English
Publication Date
6-1-2026
Journal
Nature Cancer
DOI
10.1038/s43018-026-01175-6
PMID
42286338
PMCID
PMC13309276
PubMedCentral® Posted Date
6-12-2026
PubMedCentral® Full Text Version
Post-print
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.
Keywords
Humans, Leukemia, Myeloid, Acute, Nucleophosmin, Proteogenomics, Metabolomics, Multiomics, Mutation, Biomarkers, Tumor, CCAAT-Enhancer-Binding Proteins, Molecular Targeted Therapy, Cancer genomics, Mass spectrometry, Proteomic analysis, Predictive markers, Cancer
Published Open-Access
yes
Recommended Citation
Chu, Shih-Chun A; Hsiao, Yi; Wang, Chenwei; et al., "Integrated Proteogenomic and Metabolomic Profiling of Acute Myeloid Leukemias To Identify Molecular Subtypes and Associated Therapy Targets" (2026). Faculty, Staff and Students Publications. 8330.
https://digitalcommons.library.tmc.edu/baylor_docs/8330