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TOPLINE:

Blood-based proteomic profiling of 251 inflammatory proteins in 543 newly diagnosed patients with acute myeloid leukemia (AML) identified an eight-protein signature that enhances risk stratification. Oncostatin M receptor (OSMR) emerged as the strongest independent predictor of survival, early mortality, and response to induction therapy.

METHODOLOGY:

• Researchers performed blood-based proteomic profiling of 251 inflammatory proteins in 543 newly diagnosed patients with AML presenting between January 2012 and March 2023, with a median follow-up of 26 months.
• Analysis included machine learning models through least absolute shrinkage and selection operator-Cox regression analysis to identify proteins strongly associated with overall survival.
• Validation cohorts comprised 68 consecutive newly diagnosed patients with AML from the same institution and 113 patients from Princess Margaret Cancer Centre who received standard 7 + 3 induction therapy.

TAKEAWAY:

• The Leukemia Inflammatory Risk Score (LIRS), comprising eight proteins, demonstrated superior prognostic value compared with the European LeukemiaNet 2022 risk model, with high LIRS associated with increased hazard of death (hazard ratio [HR], 6.10; 95% CI, 2.26-16.47; P < .001).
• OSMR emerged as the strongest independent predictor, with high levels associated with lower complete remission rates in both intensive (65% vs 87%; P = .0028) and non-intensive induction (48% vs 73%; P < .001).
• High OSMR levels correlated with increased early mortality at 4 weeks (12% vs 3%; P = .0016) and 8 weeks (30% vs 10%; P < .001).
• Gene set enrichment analysis revealed significant enrichment of interleukin 6-Janus kinase-signal transducer and activator of transcription (normalized enrichment score [NES], 1.82; P = .0003) and inflammatory response (NES, 1.44; P = .0036) pathways in the OSMR high group.

IN PRACTICE:

“These blood-based biomarkers could have significant clinical implications for risk stratification and prognostication in patients with newly diagnosed AML….Blood-based LIRS significantly outperformed the European LeukemiaNet (ELN) 2022 risk model and was independently prognostic of overall survival after accounting for known clinical and molecular prognostic factors,” wrote the authors of the study.

SOURCE:

The study was led by Patrick Reville, MD; Hussein Abbas, MD, PhD; and Bofei Wang, PhD, The University of Texas MD Anderson Cancer Center in Houston. It was published online in Blood.

LIMITATIONS:

According to the authors, while most results were cross-sectional, batch effects from sequencing posed challenges in defining cutoff values for clinical use. The study population was predominantly White from North America, limiting generalizability to diverse populations. Additionally, inflammatory proteins were measured only at the pretreatment timepoint, which may not represent the dynamic inflammatory proteome in bone marrow or at later timepoints including remission or relapse.

DISCLOSURES:

The study received support from the Cancer Prevention & Research Institute of Texas, Marshall Foundation Funding, and the National Institutes of Health and National Cancer Institute. Reville disclosed ties with the Lymphoma Research Foundation. Abbas reported relationships with Illumina, Alamar Biosciences, Genentech, Enzyme by Design, GlaxoSmithKline, Blueprint Medicines, Ascentage Pharma, Cogent Biosciences, and Molecular Partners.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.