Integrated proteogenomic and metabolomic profiling of acute myeloid leukemias to identify molecular subtypes and associated therapy targets - Report - MDSpire

Integrated proteogenomic and metabolomic profiling of acute myeloid leukemias to identify molecular subtypes and associated therapy targets

  • By

  • Shih-Chun A. Chu

  • Yi Hsiao

  • Chenwei Wang

  • Jennifer E. Kyle

  • Raghav Jain

  • Yamei Deng

  • Marina A. Gritsenko

  • Leanne E. Henry

  • Jonathan T. Lei

  • Yongchao Dou

  • Bahar Tercan

  • Zhiao Shi

  • Mahnoor N. Gondal

  • Chia-Feng Tsai

  • John M. Elizarraras

  • Rosalie K. Chu

  • Fengchao Yu

  • Sunil K. Joshi

  • Xiaojun Jing

  • Daniel A. Polasky

  • Karl K. Weitz

  • Ginny Xiaohe Li

  • Vanessa L. Paurus

  • Chaevien S. Clendinen

  • Athena A. Schepmoes

  • Priscila M. Lalli

  • Josie G. Eder

  • Javier E. Flores

  • Kelly G. Stratton

  • James C. Pino

  • Camilo Posso

  • Vladislav A. Petyuk

  • Tyler J. Sagendorf

  • Yuanwei Xu

  • Omar M. Ibrahim

  • Ronald J. Moore

  • Rui Zhao

  • Jin Chen

  • Matthew E. Monroe

  • Mathangi Thiagarajan

  • Galen Hostetter

  • Chelsea Newton

  • Eunkyung An

  • Ana I. Robles

  • Xu Zhang

  • Nathan J. Edwards

  • Yin Lu

  • Hui Zhang

  • Haitham Abdelhakim

  • Paul D. Piehowski

  • Mehdi Mesri

  • Richard D. Smith

  • Chandan Kumar-Sinha

  • Cristina E. Tognon

  • Jennifer Dunlap

  • Elie Traer

  • Li Ding

  • Jeffrey W. Tyner

  • Arul M. Chinnaiyan

  • Gilbert S. Omenn

  • Karin D. Rodland

  • Saravana M. Dhanasekaran

  • Sara J. C. Gosline

  • Alexey I. Nesvizhiskii

  • Bing Zhang

  • Tao Liu

  • Marcin P. Cieslik

  • June 12, 2026

  • 0 min

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Clinical Report: Comprehensive Proteogenomic and Metabolomic Analysis of AML

Overview

This study presents a multiomic atlas of acute myeloid leukemia (AML) derived from 173 treatment-naive individuals, identifying eight distinct molecular subtypes linked to specific genetic drivers and drug responses. The findings highlight the complexity of AML and the potential for advanced stratification in therapeutic development.

Background

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy with a low 5-year survival rate of 30% and high relapse rates. Current treatment strategies include intensive chemotherapy and targeted therapies for specific genetic mutations. Understanding the molecular subtypes of AML is crucial for improving treatment outcomes and developing personalized therapies.

Data Highlights

Data TypeParticipants
Genomics173
Proteomics162
Metabolomics97
Matched Normal DNA161

Key Findings

  • Identified eight distinct AML subtypes (AML-8) linking genetic drivers to molecular traits.
  • High mitochondrial content in certain proteomic AML subsets showed sensitivity to venetoclax.
  • High tumor purity was observed, averaging 79% across samples.
  • 111,993 molecular features were detected with good technical reproducibility.
  • Distinct cellular compartments were enriched with proteins harboring different types of post-translational modifications (PTMs).

Clinical Implications

The multiomic classification of AML may enhance the understanding of its clinical heterogeneity and inform the development of targeted therapies. This approach could facilitate more personalized treatment strategies based on specific molecular characteristics.

Conclusion

The comprehensive proteogenomic and metabolomic analysis of AML provides a valuable resource for future research and therapeutic development, emphasizing the need for advanced stratification in this complex disease.

Related Resources & Content

  1. Cancer Genome Atlas Research Network, The New England Journal of Medicine, 2013 -- Genomic and Epigenomic Characterization of Acute Myeloid Leukemia
  2. npj Digital Medicine, 2025 -- Machine learning-driven glycolytic subtyping and exosome-based PKM splicing modulation overcome drug resistance in hyper-glycolytic myeloid leukemia
  3. The ASCO Post, 2013 -- Molecular Landscaping of Acute Myeloid Leukemia: Are We Relearning the Past or Informing the Future?
  4. Blood Cancer Journal — Cellular Signal-Transduction Mechanisms in Acute Myeloid Leukemia Following In Vivo Combination Treatment with ATRA, Valproic Acid, and Theophylline
  5. 2025 update on MRD in acute myeloid leukemia: a consensus document from the ELN-DAVID MRD Working Party
  6. FDA approves revumenib for relapsed or refractory acute myeloid leukemia with a susceptible NPM1 mutation
  7. https://www.hematology.org/-/media/hematology/files/clinicians/guidelines/ash-guidelines-update-2025/aml-summary-of-changes-final.pdf
  8. Efficacy and safety of venetoclax plus azacitidine based regimens in the treatment of relapsed or refractory acute myeloid leukemia: a systematic review and meta-analysis - PubMed
  9. Proteogenomic analysis of NPM1-mutated AML reveals clinical heterogeneity related to differentiation states and mitochondrial metabolism - ScienceDirect

Original Source(s)

Integrated proteogenomic and metabolomic profiling of acute myeloid leukemias to identify molecular subtypes and associated therapy targets

  • by Shih-Chun A. Chu, Yi Hsiao, Chenwei Wang, Jennifer E. Kyle, Raghav Jain, Yamei Deng, Marina A. Gritsenko, Leanne E. Henry, Jonathan T. Lei, Yongchao Dou, Bahar Tercan, Zhiao Shi, Mahnoor N. Gondal, Chia-Feng Tsai, John M. Elizarraras, Rosalie K. Chu, Fengchao Yu, Sunil K. Joshi, Xiaojun Jing, Daniel A. Polasky, Karl K. Weitz, Ginny Xiaohe Li, Vanessa L. Paurus, Chaevien S. Clendinen, Athena A. Schepmoes, Priscila M. Lalli, Josie G. Eder, Javier E. Flores, Kelly G. Stratton, James C. Pino, Camilo Posso, Vladislav A. Petyuk, Tyler J. Sagendorf, Yuanwei Xu, Omar M. Ibrahim, Ronald J. Moore, Rui Zhao, Jin Chen, Matthew E. Monroe, Mathangi Thiagarajan, Galen Hostetter, Chelsea Newton, Eunkyung An, Ana I. Robles, Xu Zhang, Nathan J. Edwards, Yin Lu, Hui Zhang, Haitham Abdelhakim, Paul D. Piehowski, Mehdi Mesri, Richard D. Smith, Chandan Kumar-Sinha, Cristina E. Tognon, Jennifer Dunlap, Elie Traer, Li Ding, Jeffrey W. Tyner, Arul M. Chinnaiyan, Gilbert S. Omenn, Karin D. Rodland, Saravana M. Dhanasekaran, Sara J. C. Gosline, Alexey I. Nesvizhiskii, Bing Zhang, Tao Liu, Marcin P. Cieslik

  • June 12, 2026

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