Faculty, Staff and Student Publications

Language

English

Publication Date

1-1-2025

Journal

Frontiers in Pharmacology

DOI

10.3389/fphar.2025.1557112

PMID

40191420

PMCID

PMC11968745

PubMedCentral® Posted Date

3-21-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults and the second most common in children. Despite the introduction of targeted therapies, AML survival rates have shown limited improvement, particularly among older patients. This study explored personalized treatment strategies for AML by proposing a novel subtyping method. Through unsupervised clustering based on the enrichment scores of 14 pathways related to metabolism, immunity, DNA repair, and oncogenic signaling, we identified three AML subtypes: DNA repair (DR), immune-enriched (ImE), and immune-deprived (ImD), consistent in four independent datasets. DR is marked by high expression of DNA repair and metabolic pathways, high stemness and proliferation potential, as well as high sensitivity to chemotherapy. ImD is characterized by low expression of immune and oncogenic pathways, favorable survival prognosis, low mutation rates of RUNX1 and TP53, high homeostasis, and low migration potential. ImE exhibits high enrichment of immune and oncogenic pathways, low stemness and proliferation capacity, low homeostasis, high migration potential, and low sensitivity to chemotherapy. Our pathway enrichment-based subtyping approach would offer a promising framework for understanding the molecular heterogeneity of AML and guiding personalized treatment of this disease.

Keywords

AML, acute myeloid leukemia, pathway enrichment analysis, transcriptome (RNA-seq), drug sensitivity, subtype

Published Open-Access

yes

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