Blood-based proteomic profiling identifies OSMR as a novel biomarker of AML outcomes.

Journal: Blood
Published Date:

Abstract

Inflammation is increasingly recognized as a critical factor in acute myeloid leukemia (AML) pathogenesis. We performed blood-based proteomic profiling of 251 inflammatory proteins in 543 patients with newly diagnosed AML. Using a machine learning model, we derived an 8-protein prognostic score termed the leukemia inflammatory risk score (LIRS). Individual proteins were evaluated in multivariable Cox models, and model performance was assessed by cumulative concordance index. Findings were validated in internal and external cohorts across 2 institutions. Blood-based LIRS significantly outperformed the European LeukemiaNet 2022 risk model and was independently prognostic of overall survival after accounting for known clinical and molecular prognostic factors. Oncostatin M receptor was uniquely identified as the strongest independent predictor of survival, early mortality, and induction chemotherapy response, and further validated in an independent assay. These blood-based biomarkers could have significant clinical implications for risk stratification and prognostication in patients with newly diagnosed AML.

Authors

  • Patrick K Reville
    Division of Cancer Medicine, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Bofei Wang
    Division of Cancer Medicine, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Jennifer Marvin-Peek
    Division of Cancer Medicine, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Bin Yuan
    Division of Cancer Medicine, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Yu-An Kuo
    Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, 78712, USA.
  • Araceli Garza
    Division of Cancer Medicine, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Jessica Root
    Division of Cancer Medicine, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Wei Qiao
    Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX.
  • Andrea Arruda
    Department of Medical Biophysics, Princess Margaret Cancer Centre, Toronto, ON, Canada.
  • Ivo Veletic
    Division of Cancer Medicine, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Yiwei Liu
    School of Computer Science and Engineering, Central South University, Changsha, Hunan 410083, P.R. China.
  • Nicholas J Short
    Division of Cancer Medicine, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Courtney D DiNardo
    Department of Leukemia, MD Anderson Cancer Center, Houston, Texas, USA.
  • Tapan M Kadia
    Division of Cancer Medicine, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Naval G Daver
    Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Philip L Lorenzi
    Division of Discovery Science, Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Koji Sasaki
    Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
  • Steven Kornblau
    Division of Cancer Medicine, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Mark D Minden
    6 Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
  • Farhad Ravandi
    Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
  • Hagop M Kantarjian
    Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.
  • Hussein A Abbas
    Division of Cancer Medicine, Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX.